Clinical experience with a novel electromyographic approach to preventing phrenic nerve injury during cryoballoon ablation in atrial fibrillation.

PubMed

Mondésert, Blandine; Andrade, Jason G; Khairy, Paul; Guerra, Peter G; Dyrda, Katia; Macle, Laurent; Rivard, Léna; Thibault, Bernard; Talajic, Mario; Roy, Denis; Dubuc, Marc; Shohoudi, Azadeh

2014-08-01

Phrenic nerve palsy remains the most frequent complication associated with cryoballoon-based pulmonary vein (PV) isolation. We sought to characterize our experience using a novel monitoring technique for the prevention of phrenic nerve palsy. Two hundred consecutive cryoballoon-based PV isolation procedures between October 2010 and October 2013 were studied. In addition to standard abdominal palpation during right phrenic nerve pacing from the superior vena cava, all patients underwent diaphragmatic electromyographic monitoring using surface electrodes. Cryoablation was terminated on any perceived reduction in diaphragmatic motion or a 30% decrease in the compound motor action potential (CMAP). During right-sided ablation, a ≥30% reduction in CMAP amplitude occurred in 49 patients (24.5%). Diaphragmatic motion decreased in 30 of 49 patients and was preceded by a 30% reduction in CMAP amplitude in all. In 82% of cases, this reduction in CMAP amplitude occurred during right superior PV isolation. The baseline CMAP amplitude was 946.5±609.2 mV and decreased by 13.8±13.8% at the end of application. This decrease was more marked in the 33 PVs with a reduction in diaphragmatic motion than in those without (40.9±15.3% versus 11.3±10.5%; P<0.001). In 3 cases, phrenic nerve palsy persisted beyond the end of the procedure, with all cases recovering within 6 months. Despite the shortened application all veins were isolated. At repeat procedure the right-sided PVs reconnected less frequently than the left-sided PVs in those with phrenic nerve palsy. Electromyographic phrenic nerve monitoring using the surface CMAP is reliable, easy to perform, and offers an early warning to impending phrenic nerve injury. © 2014 American Heart Association, Inc.

AAEM case report 16. Botulism. American Association of Electrodiagnostic Medicine.

PubMed

Maselli, R A; Bakshi, N

2000-07-01

Early diagnosis of botulism is essential for effective treatment. Electrophysiologic testing can be of major help to establish a prompt diagnosis, but the classic electrodiagnostic features of botulism are often elusive. Decrement or increment of compound muscle action potential (CMAP) amplitudes to slow or fast rates of nerve stimulation are often unimpressive or totally absent. Reduction of CMAP amplitudes, denervation activity, or myopathic-like motor unit potentials in affected muscles are found more frequently but they are less specific. In general, the electrophysiologic findings taken together suggest involvement of the motor nerve terminal, which should raise the possibility of botulism. The case reported here illustrates a common clinical presentation of botulism. This study emphasizes realistic expectations of the electrodiagnostic testing, the differential diagnosis, and the potential pitfalls often encountered in the interpretation of the electrophysiologic data. Copyright 2000 American Association of Electrodiagnostic Medicine.

Optical stimulation of the facial nerve: a surgical tool?

NASA Astrophysics Data System (ADS)

Richter, Claus-Peter; Teudt, Ingo Ulrik; Nevel, Adam E.; Izzo, Agnella D.; Walsh, Joseph T., Jr.

2008-02-01

One sequela of skull base surgery is the iatrogenic damage to cranial nerves. Devices that stimulate nerves with electric current can assist in the nerve identification. Contemporary devices have two main limitations: (1) the physical contact of the stimulating electrode and (2) the spread of the current through the tissue. In contrast to electrical stimulation, pulsed infrared optical radiation can be used to safely and selectively stimulate neural tissue. Stimulation and screening of the nerve is possible without making physical contact. The gerbil facial nerve was irradiated with 250-μs-long pulses of 2.12 μm radiation delivered via a 600-μm-diameter optical fiber at a repetition rate of 2 Hz. Muscle action potentials were recorded with intradermal electrodes. Nerve samples were examined for possible tissue damage. Eight facial nerves were stimulated with radiant exposures between 0.71-1.77 J/cm2, resulting in compound muscle action potentials (CmAPs) that were simultaneously measured at the m. orbicularis oculi, m. levator nasolabialis, and m. orbicularis oris. Resulting CmAP amplitudes were 0.3-0.4 mV, 0.15-1.4 mV and 0.3-2.3 mV, respectively, depending on the radial location of the optical fiber and the radiant exposure. Individual nerve branches were also stimulated, resulting in CmAP amplitudes between 0.2 and 1.6 mV. Histology revealed tissue damage at radiant exposures of 2.2 J/cm2, but no apparent damage at radiant exposures of 2.0 J/cm2.

Primary hyperparathyroidism is associated with subclinical peripheral neural alterations.

PubMed

Diniz, Erik Trovão; Bandeira, Francisco; Lins, Otávio Gomes; Cavalcanti, Érica Nogueira Bezerra; de Arruda, Tiago Matos; Januário, Alexandre Medeiros Sampaio; Diniz, Kaisa Trovão; Marques, Thyciara Fontenele; Azevedo, Hildo

2013-01-01

Some case reports have suggested primary hyperparathyroidism (PHPT) and peripheral polyneuropathy (PPN) are associated; however, there are no reports of studies examining this possible relationship. The aim of this study was to evaluate peripheral nerve conduction in subjects with PHPT. The study involved 17 patients with PHPT. Mean patient age was 60.5 ± 12.9 years, serum calcium concentration was 11.5 ± 1.0 mg/dL, and the serum parathyroid hormone (PTH) level was 315 ± 569 pg/dL. The control group comprised 17 individuals without PHPT. The mean age of controls was 60.8 ± 12.5 years and the serum calcium concentration was 9.8 ± 0.3 mg/dL. Motor and sensory nerve conduction was assessed by electroneurography (ENG). The following ENG parameters differed significantly between the PHPT and control groups: right (R) sural sensory nerve action potential conduction velocity (52.7 ± 6.3 m/s versus 58.0 ± 8.0 m/s; P = .041); R median compound muscle action potential (CMAP) amplitude (7.4 ± 1.6 mV versus 8.9 ± 1.7 mV; P = .002); R median CMAP latency (4.3 ± 1.2 ms versus 3.6 ± 0.6 ms; P = .032); R tibial CMAP latency (4.2 ± 1.1 ms versus 3.3 ± 0.4 ms; P = .001). The neurological examination was normal in all patients. Our data demonstrate an association between PHPT and peripheral neurological alterations, consistent with subclinical sensory-motor PPN.

Magnetic stimulation of the cauda equina in the spinal canal with a flat, large round coil.

PubMed

Matsumoto, Hideyuki; Octaviana, Fitri; Terao, Yasuo; Hanajima, Ritsuko; Yugeta, Akihiro; Hamada, Masashi; Inomata-Terada, Satomi; Nakatani-Enomoto, Setsu; Tsuji, Shoji; Ugawa, Yoshikazu

2009-09-15

Magnetic round coil stimulation over the spinal enlargement activates the spinal nerves at the neuro-foramina level. However, activation of the cauda equina in the spinal canal has never been described in the literature. This study, for which 40 healthy subjects were recruited, activated the cauda equina using a round 20-cm-diameter coil designated as a Magnetic Augmented Translumbosacral Stimulation (MATS) coil. Magnetic stimulation placing the edge of the coil over the L1 and L3 spinous processes elicited compound muscle action potentials (CMAPs) from the abductor hallucis muscle. The CMAPs were compared with those elicited through high-voltage electrical stimulation. The CMAP latencies to L1 level MATS coil stimulation were not significantly different from those evoked by electrical stimulation at the same level. The CMAP latencies to L3 level MATS coil stimulation were varied in each subject. In fact, the L1 level MATS coil stimulation is considered to activate the cauda equina at the root exit site from the conus medullaris; the L3 level MATS coil stimulation activates some mid-part of the cauda equina or the distal cauda equina by spreading current. The MATS coil facilitates evaluation of spinal nerve conduction in the cauda equina.

Endotracheal Tube Electrodes to Assess Vocal Cord Motor Function During Surgery in the Cerebellopontine Angle.

PubMed

Romagna, Alexander; Rachinger, Walter; Schwartz, Christoph; Mehrkens, Jan-Hinnerk; Betz, Christian; Briegel, Josef; Schnell, Oliver; Tonn, Jörg-Christian; Schichor, Christian; Thon, Niklas

2015-09-01

The 10th cranial nerve (CN X) is at risk during surgery in the lower cerebellopontine angle (CPA). To evaluate endotracheal surface electrodes for assessment of CN X motor function during CPA surgery. Twenty patients were enrolled. Electrophysiological recordings were analyzed and retrospectively correlated with clinical, imaging, and intraoperative data. Recordings from endotracheal surface electrodes were reliable and eligible for analyses in 17 patients; in 3 patients, no surface electrode compound motor action potentials (CMAPs) could be obtained. Those patients with sufficient recordings underwent surgery in the CPA for tumors in 14 patients and for nontumor pathologies in 3 patients. In 12 patients, bipolar stimulation of motor rootlets in the CPA resulted in simultaneous CMAPs recorded from both surface electrodes and needle electrodes placed in the soft palate. Coactivation was particularly seen in patients with an intricate relationship between lower cranial nerves and tumor formations (n = 9/10). Amplitudes and latencies of vocal cord CMAPs showed high interindividual but low intraindividual variability. Parameters were not well correlated with the type of surgery (tumor vs nontumor surgery) and lower CN anatomy (displaced vs undisplaced). In 2 patients, vocal cord CMAPs were lost during tumor surgery, which was associated with postoperative dysphagia and hoarseness in 1 patient. Endotracheal surface electrodes allow identification of vocal cord motor rootlets in the CPA. Worsening of CMAP parameters might indicate functional impairment. These aspects support the use of endotracheal surface electrodes in selected patients in whom the vagus nerve might be at risk during CPA surgery.

Comparison of Systemic Toxicity between Botulinum Toxin Subtypes A1 and A2 in Mice and Rats.

PubMed

Torii, Yasushi; Goto, Yoshitaka; Nakahira, Shinji; Kozaki, Shunji; Kaji, Ryuji; Ginnaga, Akihiro

2015-06-01

The adverse events caused by botulinum toxin type A (subtype A1) product, thought to be after-effects of toxin diffusion after high-dose administration, have become serious issues. A preparation showing less diffusion in the body than existing drugs has been sought. We have attempted to produce neurotoxin derived from subtype A2 (A2NTX) with an amino acid sequence different from that of neurotoxin derived from subtype A1 (A1NTX). In this study, to investigate whether A2NTX has the potential to resolve these issues, we compared the safety of A2NTX, a progenitor toxin derived from subtype A1 (A1 progenitor toxin) and A1NTX employing the intramuscular lethal dose 50% (im LD50) in mice and rats and the compound muscle action potential (CMAP) in rats. Mouse im LD50 values for A1 progenitor toxin and A2NTX were 93 and 166 U/kg, respectively, and the rat im LD50 values were 117 and 153 U/kg, respectively. In the rat CMAP test, the dose on the contralateral side, which caused a 50% reduction in the CMAP amplitude, that is, CMAP-TD50 , was calculated as 19.0, 16.6 and 28.7 U/kg for A1 progenitor toxin, A1NTX and A2NTX, respectively. The results indicate that A2NTX is safer than A1 progenitor toxin and A1NTX. © 2014 Nordic Association for the Publication of BCPT (former Nordic Pharmacological Society).

Usefulness of intraoperative electromyographic monitoring of oculomotor and abducens nerves during skull base surgery.

PubMed

Li, Zi-Yi; Li, Ming-Chu; Liang, Jian-Tao; Bao, Yu-Hai; Chen, Ge; Guo, Hong-Chuan; Ling, Feng

2017-10-01

Intraoperative neurophysiologic monitoring of the extraocular cranial nerve (EOCN) is not commonly performed because of technical difficulty and risk, reliability of the result and predictability of the postoperative function of the EOCN. We performed oculomotor nerve (CN III) and abducens nerve (CN VI) intraoperative monitoring in patients with skull base surgery by recording the spontaneous muscle activity (SMA) and compound muscle action potential (CMAP). Two types of needle electrodes of different length were percutaneously inserted into the extraocular muscles with the free-hand technique. We studied the relationships between the SMA and CMAP and postoperative function of CN III and CN VI. A total of 23 patients were included. Nineteen oculomotor nerves and 22 abducens nerves were monitored during surgery, respectively. Neurotonic discharge had a positive predictive value of less than 50% and negative predictive value of more than 80% for postoperative CN III and CN VI dysfunction. The latency of patients with postoperative CN III dysfunction was 2.79 ± 0.13 ms, longer than that with intact CN III function (1.73 ± 0.11 ms). One patient had transient CN VI dysfunction, whose CMAP latency (2.54 ms) was longer than that of intact CN VI function (2.11 ± 0.38 ms). There was no statistically significant difference between patients with paresis and with intact function. The method of intraoperative monitoring of EOCNs described here is safe and useful to record responses of SMA and CMAP. Neurotonic discharge seems to have limited value in predicting the postoperative function of CN III and CN VI. The onset latency of CMAP longer than 2.5 ms after tumor removal is probably relevant to postoperative CN III and CN VI dysfunction. However, a definite quantitative relationship has not been found between the amplitude and stimulation intensity of CMAP and the postoperative outcome of CN III and CN VI.

Effect of botulinum-A toxin to cremaster muscle: an experimental study.

PubMed

Cakmak, Murat; Cağlayan, Fatma; Erdemoğlu, Ali Kemal; Ulusoy, Sevgi

2003-10-01

A controversy exists on the definition, etiology and treatment of the retractile testes. In the present experimental study, we aimed to show the effect of botulinum-A toxin (Botox) on cremasteric muscle of a rat, and whether it may be an alternative to surgical treatment of retractile testis. Ten Wistar rats were used in the study. By stimulating cremasteric reflex, five compound muscle action potentials (CMAP) of the right and left cremasteric muscles of each rat were recorded using surface electrodes. Intramuscular injection of botulinum-A toxin was done to the right side. Saline was injected to the left cremasteric muscles, and the left side also served as control. CMAP of the cremasteric muscles were recorded 45 days after the injection. Statistical analysis was done using Wilcoxon Signed rank test. Mean CMAP of the right side was 3.25+/-1.39 microV before the injection and 0.44+/-0.25 microV after botulinum-A toxin injection. The difference was statistically significant (p<0.05). Mean CMAP on the left side was 3.48+/-0.32 microV and 3.14+/-1.12 microV at baseline and the end of the study, respectively. The difference was not statistically significant (p>0.05). The botulinum-A toxin paralyzes the cremasteric muscles of the rats. As cremasteric hypertonicity is accepted as one of the reasons for retractile testes, botulinum-A toxin injection to cremasteric muscles may be helpful in diagnosis and may be an alternative to surgical treatment of this pathology in repeated dosages. Long-term evaluation of this paralysis is necessary.

Focal clonus elicited by electrical stimulation of the motor cortex in humans.

PubMed

Hamer, Hajo M; Lüders, Hans O; Rosenow, Felix; Najm, Imad

2002-09-01

Focal clonic seizures are a frequent epileptic phenomenon. However, there are little data about their pathomechanism. In four patients with focal epilepsy and subdural electrodes, focal clonus was elicited by electrical stimulation of the motor cortex. Three additional patients underwent intraoperative stimulation of the spinal cord. Rhythmic clonic muscle responses were elicited by cortical stimulation with 20-50 Hz. The clonus consisted of simultaneous trains of compound muscle action potentials (CMAP) in agonistic and antagonistic muscles alternating with periods of muscular silence despite continuous stimulation. Clonus frequency decreased from 4.0-8.0 Hz at 50 Hz stimulation to 3.0-3.5 Hz at 20 Hz paralleled by a prolongation of the trains of CMAP. The stimulation frequency correlated with the number of stimuli blocked during relaxation. During the stable stimulation periods, the clonus frequency decreased over time. The number of stimuli which formed a train of CMAP and which were blocked during relaxation increased towards the end of the stimulation periods. Increasing intensity of stimulation at the same frequency converted a clonic to a tonic response. There was always an 1:1 relationship between stimulus and CMAP during spinal cord stimulation. We hypothesize that during cortical stimulation, clonus is elicited by synchronous activation of pyramidal tract (PT) neurons which results in excitation of intracortical GABA(B)ergic interneurons by recurrent axon-collaterals. This leads to stepwise hyperpolarization of PT neurons intermittently suppressing the output of PT neurons despite continuous stimulation. This mechanism can explain our finding that temporal and spatial summation of the stimuli were needed for clonus generation. Copyright 2002 Elsevier Science B.V.

[Statistical (Poisson) motor unit number estimation. Methodological aspects and normal results in the extensor digitorum brevis muscle of healthy subjects].

PubMed

Murga Oporto, L; Menéndez-de León, C; Bauzano Poley, E; Núñez-Castaín, M J

Among the differents techniques for motor unit number estimation (MUNE) there is the statistical one (Poisson), in which the activation of motor units is carried out by electrical stimulation and the estimation performed by means of a statistical analysis based on the Poisson s distribution. The study was undertaken in order to realize an approximation to the MUNE Poisson technique showing a coprehensible view of its methodology and also to obtain normal results in the extensor digitorum brevis muscle (EDB) from a healthy population. One hundred fourteen normal volunteers with age ranging from 10 to 88 years were studied using the MUNE software contained in a Viking IV system. The normal subjects were divided into two age groups (10 59 and 60 88 years). The EDB MUNE from all them was 184 49. Both, the MUNE and the amplitude of the compound muscle action potential (CMAP) were significantly lower in the older age group (p< 0.0001), showing the MUNE a better correlation with age than CMAP amplitude ( 0.5002 and 0.4142, respectively p< 0.0001). Statistical MUNE method is an important way for the assessment to the phisiology of the motor unit. The value of MUNE correlates better with the neuromuscular aging process than CMAP amplitude does.

Serial neurophysiological and neurophysiological examinations for delayed facial nerve palsy in a patient with Fisher syndrome.

PubMed

Umekawa, Motoyuki; Hatano, Keiko; Matsumoto, Hideyuki; Shimizu, Takahiro; Hashida, Hideji

2017-05-27

The patient was a 47-year-old man who presented with diplopia and gait instability with a gradual onset over the course of three days. Neurological examinations showed ophthalmoplegia, diminished tendon reflexes, and truncal ataxia. Tests for anti-GQ1b antibodies and several other antibodies to ganglioside complex were positive. We made a diagnosis of Fisher syndrome. After administration of intravenous immunoglobulin, the patient's symptoms gradually improved. However, bilateral facial palsy appeared during the recovery phase. Brain MRI showed intensive contrast enhancement of bilateral facial nerves. During the onset phase of facial palsy, the amplitude of the compound muscle action potential (CMAP) in the facial nerves was preserved. During the peak phase, the facial CMAP amplitude was within the lower limit of normal values, or mildly decreased. During the recovery phase, the CMAP amplitude was normalized, and the R1 and R2 responses of the blink reflex were prolonged. The delayed facial nerve palsy improved spontaneously, and the enhancement on brain MRI disappeared. Serial neurophysiological and neuroradiological examinations suggested that the main lesions existed in the proximal part of the facial nerves and the mild lesions existed in the facial nerve terminals, probably due to reversible conduction failure.

Neurophysiological mechanism of possibly confounding peripheral activation of the facial nerve during corticobulbar tract monitoring.

PubMed

Téllez, Maria J; Ulkatan, Sedat; Urriza, Javier; Arranz-Arranz, Beatriz; Deletis, Vedran

2016-02-01

To improve the recognition and possibly prevent confounding peripheral activation of the facial nerve caused by leaking transcranial electrical stimulation (TES) current during corticobulbar tract monitoring. We applied a single stimulus and a short train of electrical stimuli directly to the extracranial portion of the facial nerve. We compared the peripherally elicited compound muscle action potential (CMAP) of the facial nerve with the responses elicited by TES during intraoperative monitoring of the corticobulbar tract. A single stimulus applied directly to the facial nerve at subthreshold intensities did not evoke a CMAP, whereas short trains of subthreshold stimuli repeatedly evoked CMAPs. This is due to the phenomenon of sub- or near-threshold super excitability of the cranial nerve. Therefore, the facial responses evoked by short trains TES, when the leaked current reaches the facial nerve at sub- or near-threshold intensity, could lead to false interpretation. Our results revealed a potential pitfall in the current methodology for facial corticobulbar tract monitoring that is due to the activation of the facial nerve by subthreshold trains of stimuli. This study proposes a new criterion to exclude peripheral activation during corticobulbar tract monitoring. The failure to recognize and avoid facial nerve activation due to leaking current in the peripheral portion of the facial nerve during TES decreases the reliability of corticobulbar tract monitoring by increasing the possibility of false interpretation. Copyright © 2015 International Federation of Clinical Neurophysiology. Published by Elsevier Ireland Ltd. All rights reserved.

Revisiting the Therapeutic Potential of Bothrops jararaca Venom: Screening for Novel Activities Using Connectivity Mapping

PubMed Central

Nicolau, Carolina Alves; Prorock, Alyson; Bao, Yongde; Neves-Ferreira, Ana Gisele da Costa; Fox, Jay William

2018-01-01

Snake venoms are sources of molecules with proven and potential therapeutic applications. However, most activities assayed in venoms (or their components) are of hemorrhagic, hypotensive, edematogenic, neurotoxic or myotoxic natures. Thus, other relevant activities might remain unknown. Using functional genomics coupled to the connectivity map (C-map) approach, we undertook a wide range indirect search for biological activities within the venom of the South American pit viper Bothrops jararaca. For that effect, venom was incubated with human breast adenocarcinoma cell line (MCF7) followed by RNA extraction and gene expression analysis. A list of 90 differentially expressed genes was submitted to biosimilar drug discovery based on pattern recognition. Among the 100 highest-ranked positively correlated drugs, only the antihypertensive, antimicrobial (both antibiotic and antiparasitic), and antitumor classes had been previously reported for B. jararaca venom. The majority of drug classes identified were related to (1) antimicrobial activity; (2) treatment of neuropsychiatric illnesses (Parkinson’s disease, schizophrenia, depression, and epilepsy); (3) treatment of cardiovascular diseases, and (4) anti-inflammatory action. The C-map results also indicated that B. jararaca venom may have components that target G-protein-coupled receptors (muscarinic, serotonergic, histaminergic, dopaminergic, GABA, and adrenergic) and ion channels. Although validation experiments are still necessary, the C-map correlation to drugs with activities previously linked to snake venoms supports the efficacy of this strategy as a broad-spectrum approach for biological activity screening, and rekindles the snake venom-based search for new therapeutic agents. PMID:29415440

Microscale Electrode Implantation during Nerve Repair: Effects on Nerve Morphology, Electromyography, and Recovery of Muscle Contractile Function

PubMed Central

Urbanchek, Melanie G; Wei, Benjamin; Egeland, Brent M; Abidian, Mohammad R; Kipke, Daryl R; Cederna, Paul S

2011-01-01

Background Our goal is to develop a peripheral nerve electrode with long-term stability and fidelity for use in nerve-machine interfaces. Microelectromechanical systems (MEMS) use silicon probes that contain multi-channel actuators, sensors, and electronics. We tested the null hypothesis that implantation of MEMS probes do not have a detrimental effect on peripheral nerve function or regeneration. Methods A rat hindlimb, peroneal nerve model was utilized in all experimental groups: a) intact nerve (Control, n= 10); b) nerve division and repair (Repair, n= 9); and c) Nerve division, insertion of MEMS probe, and repair (Repair + Probe, n=9). Nerve morphology, nerve to muscle compound action potential (CMAP) studies, walking tracks, and extensor digitorum longus (EDL) muscle function tests were evaluated following an 80 day recovery. Results Repair and Repair + Probe showed no differences in axon count, axon size, percent non-neural area, CMAP amplitude, latency, muscle mass, muscle force, or walking track scores. Though there was some local fibrosis around each MEMS probe, this did not lead to measurable detrimental effects in any anatomic or functional outcome measurements. Conclusions The lack of a significant difference between Repair and Repair + Probe groups in histology, CMAP, walking tracks, and muscle force suggests that MEMS electrodes are compatible with regenerating axons and show promise for establishing chemical and electrical interfaces with peripheral nerves. PMID:21921739

Treatment of Dysphagia with Pyridostigmine Bromide in a Patient with the Pharyngeal-Cervical-Brachial Variant of Guillain-Barré Syndrome

PubMed Central

Lee, Kwang Lae; Lim, Oh Kyung; Park, Ki Deok

2012-01-01

A 24-year-old male developed bulbar palsy, ophthalmoplegia, ptosis, and shoulder weakness bilaterally 2 weeks after he had experienced an upper respiratory infection. The electrodiagnostic study demonstrated axonal polyradiculoneuropathy. The repetitive nerve stimulation study (RNS) showed no significant decrement of the compound muscle action potentials (CMAPs). The videofluoroscopic swallowing study (VFSS) showed severe impairment of the pharyngeal phase of swallowing. He was diagnosed as having the pharyngeal-cervical-brachial variant of Guillain-Barré syndrome. The patient's dysphagia was not improved for 3 months. A follow up RNS showed a significant decrement of the CMAPs. Pyridostigmine bromide was tried to improve the dysphagia. The patient showed immediate improvement of his dysphagia on the VFSS after the trial with pyridostigmine bromide. Pyridostigmine bromide was given before each meal for 8 days and he showed continuous improvement of his dysphagia. The follow up VFSS after 3 months showed complete recovery of dysphagia. PMID:22506249

Treatment of Dysphagia with pyridostigmine bromide in a patient with the pharyngeal-cervical-brachial variant of guillain-barré syndrome.

PubMed

Lee, Kwang Lae; Lim, Oh Kyung; Lee, Ju Kang; Park, Ki Deok

2012-02-01

A 24-year-old male developed bulbar palsy, ophthalmoplegia, ptosis, and shoulder weakness bilaterally 2 weeks after he had experienced an upper respiratory infection. The electrodiagnostic study demonstrated axonal polyradiculoneuropathy. The repetitive nerve stimulation study (RNS) showed no significant decrement of the compound muscle action potentials (CMAPs). The videofluoroscopic swallowing study (VFSS) showed severe impairment of the pharyngeal phase of swallowing. He was diagnosed as having the pharyngeal-cervical-brachial variant of Guillain-Barré syndrome. The patient's dysphagia was not improved for 3 months. A follow up RNS showed a significant decrement of the CMAPs. Pyridostigmine bromide was tried to improve the dysphagia. The patient showed immediate improvement of his dysphagia on the VFSS after the trial with pyridostigmine bromide. Pyridostigmine bromide was given before each meal for 8 days and he showed continuous improvement of his dysphagia. The follow up VFSS after 3 months showed complete recovery of dysphagia.

Visualization of the diaphragm muscle with ultrasound improves diagnostic accuracy of phrenic nerve conduction studies.

PubMed

Johnson, Nicholas E; Utz, Michael; Patrick, Erica; Rheinwald, Nicole; Downs, Marlene; Dilek, Nuran; Dogra, Vikram; Logigian, Eric L

2014-05-01

Evaluation of phrenic neuropathy (PN) with phrenic nerve conduction studies (PNCS) is associated with false negatives. Visualization of diaphragmatic muscle twitch with diaphragm ultrasound (DUS) when performing PNCS may help to solve this problem. We performed bilateral, simultaneous DUS-PNCS in 10 healthy adults and 12 patients with PN. The amplitude of the diaphragm compound muscle action potential (CMAP) (on PNCS) and twitch (on DUS) was calculated. Control subjects had <38% side-to-side asymmetry in twitch amplitude (on DUS) and 53% asymmetry in phrenic CMAP (on PCNS). In the 12 patients with PN, 12 phrenic neuropathies were detected. Three of these patients had either significant side-to-side asymmetry or absolute reduction in diaphragm movement that was not detected with PNCS. There were no cases in which the PNCS showed an abnormality but the DUS did not. The addition of DUS to PNCS enhances diagnostic accuracy in PN. Copyright © 2013 Wiley Periodicals, Inc.

Assessing Hand Muscle Structural Modifications in Chronic Stroke.

PubMed

Zong, Ya; Shin, Henry H; Wang, Ying-Chih; Li, Sheng; Zhou, Ping; Li, Xiaoyan

2018-01-01

The purpose of the study is to assess poststroke muscle structural alterations by examining muscular electrical conductivity and inherent electrophysiological properties. In particular, muscle impedance and compound muscle action potentials (CMAP) were measured from the hypothenar muscle bilaterally using the electrical impedance myography and the electrophysiological techniques, respectively. Significant changes of muscle impedance were observed in the paretic muscle compared with the contralateral side (resistance: paretic: 27.54 ± 0.97 Ω, contralateral: 25.46 ± 0.91 Ω, p  < 0.05; phase angle: paretic: 8.81 ± 0.61°, contralateral: 10.79 ± 0.69°, p  < 0.05). In addition, impedance changes correlated moderately with the CMAP amplitude in the paretic hand (phase angle: r  = 0.66, p  < 0.05; reactance: r  = 0.58, p  < 0.05). The study discloses significant muscle rearrangements as a result of fiber loss or atrophy, fat infiltration or impaired membrane integrity in chronic stroke.

Role of Kabat physical rehabilitation in Bell's palsy: a randomized trial.

PubMed

Barbara, Maurizio; Antonini, Giovanni; Vestri, Annarita; Volpini, Luigi; Monini, Simonetta

2010-01-01

When applied at an early stage, Kabat's rehabilitation was shown to provide a better and faster recovery rate in comparison with non-rehabilitated patients. To assess the validity of an early rehabilitative approach to Bell's palsy patients. A randomized study involved 20 consecutive patients (10 males, 10 females; aged 35-42 years) affected by Bell's palsy, classified according to the House-Brackmann (HB) grading system and grouped on the basis of undergoing or not early physical rehabilitation according to Kabat, i.e. a proprioceptive neuromuscular rehabilitation. The evaluation was carried out by measuring the amplitude of the compound motor action potential (CMAP), as well as by observing the initial and final HB grade, at days 4, 7 and 15 after onset of facial palsy. Patients belonging to the rehabilitation group clearly showed an overall improvement of clinical stage at the planned final observation, i.e. 15 days after onset of facial palsy, without presenting greater values of CMAP.

Presymptomatic electrophysiological tests predict clinical onset and survival in SOD1(G93A) ALS mice.

PubMed

Mancuso, Renzo; Osta, Rosario; Navarro, Xavier

2014-12-01

We assessed the predictive value of electrophysiological tests as a marker of clinical disease onset and survival in superoxide-dismutase 1 (SOD1)(G93A) mice. We evaluated the accuracy of electrophysiological tests in differentiating transgenic versus wild-type mice. We made a correlation analysis of electrophysiological parameters and the onset of symptoms, survival, and number of spinal motoneurons. Presymptomatic electrophysiological tests show great accuracy in differentiating transgenic versus wild-type mice, with the most sensitive parameter being the tibialis anterior compound muscle action potential (CMAP) amplitude. The CMAP amplitude at age 10 weeks correlated significantly with clinical disease onset and survival. Electrophysiological tests increased their survival prediction accuracy when evaluated at later stages of the disease and also predicted the amount of lumbar spinal motoneuron preservation. Electrophysiological tests predict clinical disease onset, survival, and spinal motoneuron preservation in SOD1(G93A) mice. This is a methodological improvement for preclinical studies. © 2014 Wiley Periodicals, Inc.

Axonal Dysfunction Precedes Motor Neuronal Death in Amyotrophic Lateral Sclerosis

PubMed Central

Iwai, Yuta; Shibuya, Kazumoto; Misawa, Sonoko; Sekiguchi, Yukari; Watanabe, Keisuke; Amino, Hiroshi; Kuwabara, Satoshi

2016-01-01

Wide-spread fasciculations are a characteristic feature in amyotrophic lateral sclerosis (ALS), suggesting motor axonal hyperexcitability. Previous excitability studies have shown increased nodal persistent sodium conductances and decreased potassium currents in motor axons of ALS patients, both of the changes inducing hyperexcitability. Altered axonal excitability potentially contributes to motor neuron death in ALS, but the relationship of the extent of motor neuronal death and abnormal excitability has not been fully elucidated. We performed multiple nerve excitability measurements in the median nerve at the wrist of 140 ALS patients and analyzed the relationship of compound muscle action potential (CMAP) amplitude (index of motor neuronal loss) and excitability indices, such as strength-duration time constant, threshold electrotonus, recovery cycle and current-threshold relationships. Compared to age-matched normal controls (n = 44), ALS patients (n = 140) had longer strength-duration time constant (SDTC: a measure of nodal persistent sodium current; p < 0.05), greater threshold changes in depolarizing threshold electrotonus (p < 0.05) and depolarizing current threshold relationship (i.e. less accommodation; (p < 0.05), greater superexcitability (a measure of fast potassium current; p < 0.05) and reduced late subexcitability (a measure of slow potassium current; p < 0.05), suggesting increased persistent sodium currents and decreased potassium currents. The reduced potassium currents were found even in the patient subgroups with normal CMAP (> 5mV). Regression analyses showed that SDTC (R = -0.22) and depolarizing threshold electrotonus (R = -0.22) increased with CMAP decline. These findings suggest that motor nerve hyperexcitability occurs in the early stage of the disease, and precedes motor neuronal loss in ALS. Modulation of altered ion channel function could be a treatment option for ALS. PMID:27383069

Decreased muscle endurance associated with diabetic neuropathy may be attributed partially to neuromuscular transmission failure

PubMed Central

Kimpinski, Kurt; Doherty, Timothy J.; Rice, Charles L.

2015-01-01

Diabetic polyneuropathy (DPN) can cause muscle atrophy, weakness, contractile slowing, and neuromuscular transmission instability. Our objective was to assess the response of the impaired neuromuscular system of DPN in humans when stressed with a sustained maximal voluntary contraction (MVC). Baseline MVC and evoked dorsiflexor contractile properties were assessed in DPN patients (n = 10) and controls (n = 10). Surface electromyography was used to record tibialis anterior evoked maximal compound muscle action potentials (CMAPs) and neuromuscular activity during MVCs. Participants performed a sustained isometric dorsiflexion MVC for which task termination was determined by the inability to sustain ≥60% MVC torque. The fatigue protocol was immediately followed by a maximal twitch, with additional maximal twitches and MVCs assessed at 30 s and 2 min postfatigue. DPN patients fatigued ∼21% more quickly than controls (P < 0.05) and featured less relative electromyographic activity during the first one-third of the fatigue protocol compared with controls (P < 0.05). Immediately following fatigue, maximal twitch torque was reduced similarly (∼20%) in both groups, and concurrently CMAPs were reduced (∼12%) in DPN patients, whereas they were unaffected in controls (P > 0.05). Twitch torque and CMAP amplitude recovered to baseline 30 s postfatigue. Additionally, at 30 s postfatigue, both groups had similar (∼10%) reductions in MVC torque relative to baseline, and MVC strength recovered by 2 min postfatigue. We conclude DPN patients possess less endurance than controls, and neuromuscular transmission failure may contribute to this greater fatigability. PMID:25663671

Comparative study of biological activity of four botulinum toxin type A preparations in mice.

PubMed

Chung, Myung Eun; Song, Dae Heon; Park, Joo Hyun

2013-01-01

Units of available botulinum toxin preparations are not interchangeable, and the dose-conversion ratios between such preparations remain controversial. To compare the efficacy and safety of four botulinum toxin type A preparations. Murine gastrocnemius compound muscle action potentials (CMAPs) were recorded before and after injecting the four botulinum toxin preparations (onabotulinumtoxinA, abobotulinumtoxinA, new botulinum toxin, and incobotulinumtoxinA). In all preparations, CMAP amplitudes decreased until 4 days after receiving the injection and then gradually recovered. On postinjection day 84, the amplitudes returned to baseline in all groups except the high-dose groups. CMAP amplitude in the contralateral limb also decreased up to postinjection days 4 to 7 and then gradually returned to baseline by postinjection day 28. The dose-conversion ratio between onabotulinumtoxinA and abobotulinumtoxinA was determined to be 1:2.6; previous reports of 1:3 were considered too high. A dose-conversion ratio between onabotulinumtoxinA and new botulinum toxin of 1:1 was deemed appropriate. OnabotulinumtoxinA and incobotulinumtoxinA demonstrated a dose-conversion ratio of 1:1.07. The efficacy of incobotulinumtoxinA was slightly lower than that of onabotulinumtoxinA. These dose-conversion ratios are applicable solely from an efficacy standpoint and not for safety. This study was conducted in mice, so it may not translate perfectly to human applications. © 2012 by the American Society for Dermatologic Surgery, Inc. Published by Wiley Periodicals, Inc.

[Decrement pattern of M-response amplitude in the low-frequency repetitive nerve stimulation in the muscles of patients with myasthenia gravis and Lambert-Eaton myasthenic syndrome].

PubMed

Tumurov, D A; Sanadze, A G

To investigate the pattern of decrement in the muscles of patients with myasthenia gravis (MG) and Lambert-Eaton myasthenic syndrome (LEMS). Twenty-seven patients with MG and 39 patients with LEMS were studied using low frequency repetitive nerve stimulation (3/ sec). The decrease of safety factor of neuromuscular transmission was equal in both groups. At the same time, a significant difference in the decrease of pattern of the amplitude compound of muscle action potential (CMAP) was found. In LEMS, by contrast with MG, another sequence of amplitude variability of CMAP from the second stimulus to the first and from the fifth stimulus to the fourth was noted. In LEMS patients, progressive decrement, manifesting by increasing ratios of late A9/A1 to early A4/A1 was found, whereas the MG patients showed retrogressive decrement expressed by the reduction in decrement ratio (from late to early). These differences reflect the mechanisms and status of acetylcholine mobilization and release from the axon terminal.

Recovery of sensorimotor function and activities of daily living after cervical spinal cord injury: the influence of age.

PubMed

Wirz, Markus; Dietz, Volker

2015-02-01

This retrospective study was designed to examine the influence of age on the outcome of motor function and activities of daily living (ADLs) in patients with a cervical spinal cord injury (SCI). The study is based on the data registry of the European Multicenter Study of Spinal Cord Injury (EMSCI) study group. Initial upper-extremity motor score (UEMS) and its change over 5 months, as well as the initial Spinal Cord Independence Measure (SCIM) score, did not differ between younger adults (20-39 years) and elderly (60-79 years) patients. However, the change in SCIM score over 5 months was significantly greater in the younger patient group. Initial UEMS, SCIM, and ulnar compound motor action potentials (CMAP), reflecting peripheral nerve damage (motoneurons and roots), were significantly greater in incomplete, compared to complete, SCI, regardless of age group. The initial assessment of UEMS in combination with CMAP recordings allows an early prediction of ADLs outcomes in both younger adults and elderly subjects. The impaired translation of gain in motor score into increased ADL independence in elderly patients requires specifically tailored rehabilitation programs.

Action strategy paper : climate change and energy

DOT National Transportation Integrated Search

2008-10-01

This strategy paper considers how the Chicago Metropolitan Agency for Planning (CMAP) might incorporate goals to reduce greenhouse gas (GHG) emissions, prepare for climate change impacts on transportation systems, and reduce energy with in the GO TO ...

Measuring of the compensation of a nerve root in a cervical schwannoma: a case report.

PubMed

Saiki, Masahiko; Taguchi, Toshihiko; Kaneko, Kazuo; Toyota, Kouichiro; Kato, Yoshihiko; Li, Zhenglin; Kawai, Shinya

2003-01-01

A 64-year-old woman experienced numbness and hypesthesia of the right C6 dermatome a year ago. Enhanced magnetic resonance imaging of the cervical spine revealed an enhanced tumor continuing into the foramen from the spinal cord at the C5/6 intervertebral level. It was thought to be an Eden type 2 schwannoma. Right unilateral laminectomy was performed on C5. The tumor was present in the intradural area and arose from the right C6 anterior root. Compound muscle action potentials (CMAPs) from the deltoid, biceps, and extensor carpi radial (ECR) muscles were recorded following electric cervical nerve root stimulation (0.2 ms duration, and 7 mA intensity). CMAPs of large amplitude were obtained from the deltoid, biceps, and ECR muscles following C5 root stimulation, but those following C6 root stimulation were small. As a result it was determined that the right C6 root was not associated with the nerve distribution for these muscles, so it was resected en bloc with the tumor. No apparent loss of motor function was observed. Standard needle electromyography showed no denervation potentials or decrease in motor unit potentials in either the deltoid or biceps muscles. Intraoperative investigation for compensation of nerve root is clinically useful for determining whether resection of a nerve root results in muscle weakness after surgery for a cervical schwannoma.

Intraoperative monitoring of lower cranial nerves in skull base surgery: technical report and review of 123 monitored cases.

PubMed

Topsakal, Cahide; Al-Mefty, Ossama; Bulsara, Ketan R; Williford, Veronica S

2008-01-01

The fundamental goal of skull base surgery is tumor removal with preservation of neurological function. Injury to the lower cranial nerves (LCN; CN 9-12) profoundly affects a patient's quality of life. Although intraoperative cranial nerve monitoring (IOM) is widely practiced for other cranial nerves, literature addressing the LCN is scant. We examined the utility of IOM of the LCN in a large patient series. One hundred twelve patients underwent 123 skull base operations with IOM between January 1994 to December 1999. The vagus nerve (n=37), spinal accessory nerve (n=118), and the hypoglossal nerve (n=83) were monitored intraoperatively. Electromyography (EMG) and compound muscle action potentials (CMAP) were recorded from the relevant muscles after electrical stimulation. This data was evaluated retrospectively. Patients who underwent IOM tended to have larger tumors with more intricate involvement of the lower cranial nerves. Worsening of preoperative lower cranial nerve function was seen in the monitored and unmonitored groups. With the use of IOM in the high risk group, LCN injury was reduced to a rate equivalent to that of the lower risk group (p>0.05). The immediate feedback obtained with IOM may prevent injury to the LCN due to surgical manipulation. It can also help identify the course of a nerve in patients with severely distorted anatomy. These factors may facilitate gross total tumor resection with cranial nerve preservation. The incidence of high false positive and negative CMAP and the variability in CMAP amplitude and threshold can vary depending on individual and technical factors.

Comparison of Globally Complete Versions of GPCP and CMAP Monthly Precipitation Analyses

NASA Technical Reports Server (NTRS)

Curtis, Scott; Adler, Robert; Huffman, George

1998-01-01

In this study two global observational precipitation products, namely the Global Precipitation Climatology Project's (GPCP) community data set and CPC's Merged Analysis of Precipitation (CMAP), are compared on global to regional scales in the context of the different satellite and gauge data inputs and merger techniques. The average annual global precipitation rates, calculated from data common in regions/times to both GPCP and CMAP, are similar for the two. However, CMAP is larger than GPCP in the tropics because: (1) CMAP values in the tropics are adjusted month-by month to atoll gauge data in the West Pacific, which are greater than any satellite observations used; and (2) CMAP is produced from a linear combination of data inputs, which tends to give higher values than the microwave emission estimates alone to which the inputs are adjusted in the GPCP merger over the ocean. The CMAP month-to-month adjustment to the atolls also appears to introduce temporal variations throughout the tropics which are not detected by satellite-only products. On the other hand, GPCP is larger than CMAP in the high-latitude oceans, where CMAP includes the scattering based microwave estimates which are consistently smaller than the emission estimates used in both techniques. Also, in the polar regions GPCP transitions from the emission microwave estimates to the larger TOVS-based estimates. Finally, in high-latitude land areas GPCP can be significantly larger than CMAP because GPCP attempts to correct the gauge estimates for errors due to wind loss effects.

Delayed repair of the peripheral nerve: a novel model in the rat sciatic nerve.

PubMed

Wu, Peng; Spinner, Robert J; Gu, Yudong; Yaszemski, Michael J; Windebank, Anthony J; Wang, Huan

2013-03-30

Peripheral nerve reconstruction is seldom done in the acute phase of nerve injury due to concomitant injuries and the uncertainty of the extent of nerve damage. A proper model that mimics true clinical scenarios is critical but lacking. The aim of this study is to develop a standardized, delayed sciatic nerve repair model in rats and validate the feasibility of direct secondary neurrorraphy after various delay intervals. Immediately or 1, 4, 6, 8 and 12 weeks after sciatic nerve transection, nerve repair was carried out. A successful tension-free direct neurorraphy (TFDN) was defined when the gap was shorter than 4.0 mm and the stumps could be reapproximated with 10-0 stitches without detachment. Compound muscle action potential (CMAP) was recorded postoperatively. Gaps between the two nerve stumps ranged from 0 to 9 mm, the average being 1.36, 2.85, 3.43, 3.83 and 6.4 mm in rats with 1, 4, 6, 8 and 12 week delay, respectively. The rate of successful TFDN was 78% overall. CMAP values of 1 and 4 week delay groups were not different from the immediate repair group, whereas CMAP amplitudes of 6, 8 and 12 week delay groups were significantly lower. A novel, standardized delayed nerve repair model is established. For this model to be sensitive, the interval between nerve injury and secondary repair should be at least over 4 weeks. Thereafter the longer the delay, the more challenging the model is for nerve regeneration. The choice of delay intervals can be tailored to meet specific requirements in future studies. Copyright © 2013 Elsevier B.V. All rights reserved.

Correlations between the clinical, histological and neurophysiological examinations in patients before and after parotid gland tumor surgery: verification of facial nerve transmission.

PubMed

Wiertel-Krawczuk, Agnieszka; Huber, Juliusz; Wojtysiak, Magdalena; Golusiński, Wojciech; Pieńkowski, Piotr; Golusiński, Paweł

2015-05-01

Parotid gland tumor surgery sometimes leads to facial nerve paralysis. Malignant more than benign tumors determine nerve function preoperatively, while postoperative observations based on clinical, histological and neurophysiological studies have not been reported in detail. The aims of this pilot study were evaluation and correlations of histological properties of tumor (its size and location) and clinical and neurophysiological assessment of facial nerve function pre- and post-operatively (1 and 6 months). Comparative studies included 17 patients with benign (n = 13) and malignant (n = 4) tumors. Clinical assessment was based on House-Brackmann scale (H-B), neurophysiological diagnostics included facial electroneurography [ENG, compound muscle action potential (CMAP)], mimetic muscle electromyography (EMG) and blink-reflex examinations (BR). Mainly grade I of H-B was recorded both pre- (n = 13) and post-operatively (n = 12) in patients with small (1.5-2.4 cm) benign tumors located in superficial lobes. Patients with medium size (2.5-3.4 cm) malignant tumors in both lobes were scored at grade I (n = 2) and III (n = 2) pre- and mainly VI (n = 4) post-operatively. CMAP amplitudes after stimulation of mandibular marginal branch were reduced at about 25 % in patients with benign tumors after surgery. In the cases of malignant tumors CMAPs were not recorded following stimulation of any branch. A similar trend was found for BR results. H-B and ENG results revealed positive correlations between the type of tumor and surgery with facial nerve function. Neurophysiological studies detected clinically silent facial nerve neuropathy of mandibular marginal branch in postoperative period. Needle EMG, ENG and BR examinations allow for the evaluation of face muscles reinnervation and facial nerve regeneration.

Serial electrophysiological findings in Guillain-Barré syndrome not fulfilling AIDP or AMAN criteria.

PubMed

Hosokawa, Takafumi; Nakajima, Hideto; Unoda, Kiichi; Yamane, Kazushi; Doi, Yoshimitsu; Ishida, Shimon; Kimura, Fumiharu; Hanafusa, Toshiaki

2016-09-01

Guillain-Barré syndrome (GBS) is categorized into two major subtypes: acute inflammatory demyelinating polyneuropathy (AIDP) and acute motor axonal neuropathy (AMAN). However, a proportion of patients are electrophysiologically unclassified because of electrophysiological findings that do not fulfil AIDP or AMAN criteria, and underlying pathophysiological mechanisms and lesion distributions of unclassified patients are not well defined. The aims of this study are to elucidate disease pathophysiology and lesion distribution in unclassified patients. We retrospectively studied 48 consecutive GBS patients. Patients were classified on the basis of initial electrophysiological findings according to Ho's criteria. Clinical and serial electrophysiological examinations of unclassified patients were conducted. Twelve (25 %) GBS patients were unclassified. All unclassified patients were able to walk independently at 21 days after onset. No unclassified patients, except one patient with diabetes mellitus, had sensory nerve involvement. Eight patients underwent a follow-up study within 15 days of the initial study. Distal motor latencies (DMLs) of the left median motor nerve were found to be significantly and uniformly decreased compared with initial studies (p = 0.008). DMLs (p < 0.0001) and distal compound action potential (CMAP) durations (p = 0.002) of all nerves were significantly decreased, and distal CMAP amplitudes (p = 0.026) significantly increased compared with initial studies. In unclassified GBS patients, DML values during initial electrophysiological studies would be prolonged compared with expected values in the same patient unaffected by GBS and later improve rapidly with increased distal CMAP amplitudes without the development of excessive temporal dispersions. Lesions are also present in distal nerve segments caused by reversible conduction failure.

Concept Mapping Using Cmap Tools to Enhance Meaningful Learning

NASA Astrophysics Data System (ADS)

Cañas, Alberto J.; Novak, Joseph D.

Concept maps are graphical tools that have been used in all facets of education and training for organizing and representing knowledge. When learners build concept maps, meaningful learning is facilitated. Computer-based concept mapping software such as CmapTools have further extended the use of concept mapping and greatly enhanced the potential of the tool, facilitating the implementation of a concept map-centered learning environment. In this chapter, we briefly present concept mapping and its theoretical foundation, and illustrate how it can lead to an improved learning environment when it is combined with CmapTools and the Internet. We present the nationwide “Proyecto Conéctate al Conocimiento” in Panama as an example of how concept mapping, together with technology, can be adopted by hundreds of schools as a means to enhance meaningful learning.

Botulinum toxin type A for the treatment of sialorrhoea in amyotrophic lateral sclerosis: a clinical and neurophysiological study.

PubMed

Gilio, Francesca; Iacovelli, Elisa; Frasca, Vittorio; Gabriele, Maria; Giacomelli, Elena; Picchiori, Floriana; Soldo, Pietro; Cipriani, Anna Maria; Ruoppolo, Giovanni; Inghilleri, Maurizio

2010-08-01

Botulinum toxin type A (BoNT/A) has been proposed as an alternative treatment for sialorrhoea in patients with amyotrophic lateral sclerosis (ALS). In an open-label prospective study, BoNT/A was injected into the parotid glands bilaterally using anatomic landmarks in 26 ALS patients with bulbar symptoms. Two weeks after injection the severity of sialorrhoea and the related disability were evaluated subjectively and objectively. A group of healthy subjects acted as controls for saliva production. Patients also underwent electrophysiological tests to evaluate possible toxin effects in the nearby non-injected muscles by comparing the amplitude of compound motor action potentials (cMAPs) elicited by electrical stimulation and recorded from the orbicularis oculi and masseter muscles. After BoNT/A injections, of the 26 patients treated, 23 reported that the severity of sialorrhoea improved and the disabling symptoms diminished. Cotton roll weight also decreased after BoNT/A injection, suggesting a reduction in saliva production. Two patients complained of dry mouth. BoNT/A injection left the cMAP amplitude unchanged, suggesting that botulinum toxin does not significantly affect the non-injected facial and masticatory muscles. In conclusion, intraparotid anatomically-guided BoNT/A injection is an effective, easy, and safe treatment for sialorrhoea in patients with bulbar symptoms related to ALS.

Electrophysiological study for comparing the effect of biological activity between type A botulinum toxins in rat gastrocnemius muscle.

PubMed

Kim, C-S; Jang, W S; Son, I P; Nam, S H; Kim, Y I; Park, K Y; Kim, B J; Kim, M N

2013-09-01

New cosmetic applications and products based on the effects of botulinum toxin (BTX) treatment have stimulated demand for this class of natural compounds. This demand generates the need for appropriate standardized protocols to test and compare the effectiveness of new BTX preparations. Based on the previously described electrophysiological methods, we measured and compared the inhibitory effects of two BTX type A (BTX-A) preparations on neuromuscular transmission through split-body test. The effectiveness was evaluated in terms of the compound muscle action potential (CMAP) and conduction velocity after BTX-A injection. We used a split-body method to compare two different BTX-As in the rat. Based on the changes in the CMAP, the two different BTX-As induced paralytic effect on the rat tibialis anterior muscle. However, the two different BTX-A preparations did not differ significantly in effectiveness and did not induce a delay in conduction velocity. The new BTX-A preparation used in this electrophysiological study had similar effect compared with the previously marketed BTX-A.[AQ: Please approve the edits made to the sentence "The new BTX-A preparation…") We propose that a split-body electrophysiological protocol will be useful in establishing the comparative effectiveness of new BTX products.

Effects of treadmill running on rat gastrocnemius function following botulinum toxin A injection.

PubMed

Tsai, Sen-Wei; Chen, Chun-Jung; Chen, Hsiao-Lin; Chen, Chuan-Mu; Chang, Yin-Yi

2012-02-01

Exercise can improve and maintain neural or muscular function, but the effects of exercise in physiological adaptation to paralysis caused by botulinum toxin A has not been well studied. Twenty-four rats were randomly assigned into control and treadmill groups. The rats assigned to the treadmill group were trained on a treadmill three times per week with the running speed set at 15 m/min. The duration of training was 20 min/session. Muscle strength, nerve conduction study and sciatic functional index (SFI) were used for functional analysis. Treadmill training improved the SFI at 2, 3, and 4 weeks (p = 0.01, 0.004, and 0.01, respectively). The maximal contraction force of the gastrocnemius muscle in the treadmill group was greater than in the control group (p < 0.05). The percentage of activated fibers was higher in the treadmill botox group than the percentage for the control botox group, which was demonstrated by differences in amplitude and area of compound muscle action potential (CMAP) under the curve between the groups (p < 0.05). After BoNT-A injection, treadmill improved the physiological properties of muscle contraction strength, CMAP amplitude, and the recovery of SFI. Copyright © 2011 Orthopaedic Research Society.

Concept Map Value Propagation for Tactical Intelligence

DTIC Science & Technology

2007-06-01

meaningful diagrams: KMap, SmartDraw , MindGenius, and so on. However, CmapTools is the package we are using for this project. The software , produced by the...Cmap, driven by expected variability in the value of a datum and cost to get a new value. We use the CmapTools software developed with DoD support at... software developed with DoD support at the Institute of Human and Machine Cognition as a structural basis for creating and assessing tactical Cmaps. The

Histopathology of cryoballoon ablation-induced phrenic nerve injury.

PubMed

Andrade, Jason G; Dubuc, Marc; Ferreira, Jose; Guerra, Peter G; Landry, Evelyn; Coulombe, Nicolas; Rivard, Lena; Macle, Laurent; Thibault, Bernard; Talajic, Mario; Roy, Denis; Khairy, Paul

2014-02-01

Hemi-diaphragmatic paralysis is the most common complication associated with cryoballoon ablation for atrial fibrillation, yet the histopathology of phrenic nerve injury has not been well described. A preclinical randomized study was conducted to characterize the histopathology of phrenic nerve injury induced by cryoballoon ablation and assess the potential for electromyographic (EMG) monitoring to limit phrenic nerve damage. Thirty-two dogs underwent cryoballoon ablation of the right superior pulmonary vein with the objective of inducing phrenic nerve injury. Animals were randomized 1:1 to standard monitoring (i.e., interruption of ablation upon reduction in diaphragmatic motion) versus EMG guidance (i.e., cessation of ablation upon a 30% reduction in the diaphragmatic compound motor action potential [CMAP] amplitude). The acute procedural endpoint was achieved in all dogs. Phrenic nerve injury was characterized by Wallerian degeneration, with subperineural injury to large myelinated axons and evidence of axonal regeneration. The degree of phrenic nerve injury paralleled the reduction in CMAP amplitude (P = 0.007). Animals randomized to EMG guidance had a lower incidence of acute hemi-diaphragmatic paralysis (50% vs 100%; P = 0.001), persistent paralysis at 30 days (21% vs 75%; multivariate odds ratio 0.12, 95% confidence interval [0.02, 0.69], P = 0.017), and a lesser severity of histologic injury (P = 0.001). Mature pulmonary vein ablation lesion characteristics, including circumferentiality and transmurality, were similar in both groups. Phrenic nerve injury induced by cryoballoon ablation is axonal in nature and characterized by Wallerian degeneration, with potential for recovery. An EMG-guided approach is superior to standard monitoring in limiting phrenic nerve damage. © 2013 Wiley Periodicals, Inc.

CMap 1.01: a comparative mapping application for the internet

USDA-ARS?s Scientific Manuscript database

CMap is a web-based tool for displaying and comparing maps of any type and from any species. A user can compare an unlimited number of maps, view pair-wise comparisons of known correspondences, and search for maps or for features by name, species, type and accession. CMap is freely available, can ...

Propulsion simulation test technique for V/STOL configurations

NASA Technical Reports Server (NTRS)

Bailey, R. O.; Smith, S. C.; Bustie, J. B.

1983-01-01

Ames Research Center is developing the technology for turbine-powered jet engine simulators so that airframe/propulsion system interactions on V/STOL fighter aircraft and other highly integrated configurations can be studied. This paper describes the status of the compact multimission aircraft propulsion simulator (CMAPS) technology. Three CMAPS units have accumulated a total of 340 hr during approximately 1-1/2 yr of static and wind-tunnel testing. A wind-tunnel test of a twin-engine CMAPS-equipped close-coupled canard-wing V/STOL model configuration with nonaxisymmetric nozzles was recently completed. During this test approximately 140 total hours were logged on two CMAPS units, indicating that the rotating machinery is reliable and that the CMAPS and associated control system provide a usable test tool. However, additional development is required to correct a drive manifold O-ring problem that limits the engine-pressure-ratio (EPR) to approximately 3.5.

Demonstration of ameliorative effect of lacosamide: in a rat model of sepsis-induced critical illness polyneuropathy.

PubMed

Solmaz, Volkan; Aksoy, Dürdane; Yılmaz, Mustafa; Eser, Enes; Erbas, Oytun

2015-09-01

Critical illness neuropathy (CIN) is a condition that may occur in diseases with severe systemic response, particularly in sepsis. The aim of this study is to investigate the potential anti-inflammatory and lipid-peroxidation inhibiting activities of lacosamide by measuring tumour necrotizing factor-alpha (TNF-alpha), C-reactive protein (CRP), malondialdehyde (MDA) and white blood cells (WBC) using electroneuromyography (ENMG) in rats with sepsis-induced critical illness neuropathy (SICIN). Cecal ligation and puncture (CLP) procedure was performed on 39 rats to induce a sepsis model. The study groups were designed as follows: Group 1: normal (nonoperative); Group 2: (sham-operated); Group 3: CLP (untreated group); Group 4: CLP and lacosamide 20 mg/kg; Group 5: CLP and lacosamide 40 mg/kg. TNF-alpha, C reactive protein, MDA and WBC levels was measured and compound muscle action potential (CMAP) distal latans, amplitudes were measured by using ENMG in rats with SICIN. When untreated sepsis group was compared with both control and sham groups, CMAP amplitudes and latans were significantly lower (P < 000.1). When CLP, CLP+lacosamide 20 mg/kg and CLP+lacosamide 40 mg/kg groups were compared, plasma levels of TNF-alpha and MDA were significantly higher in the untreated CLP group (F = 12.74, P < 0.0001), (F = 19.43, P < 0.05). In the CLP+lacosamide 40 mg/kg group, CRP levels were significantly lower only compared to the CLP group (P < 0.001). We have showed that lacosamide may have beneficial effects on early SICIN by its potential anti-inflammatory and lipid peroxidation inhibiting activities; however, further comprehensive studies are required to clarify these effects.

Evaluation of a patient with suspected chronic demyelinating polyneuropathy.

PubMed

Jani-Acsadi, Agnes; Lewis, Richard A

2013-01-01

Demyelinating neuropathies are typically characterized by physiological slowing of conduction velocity and pathologically by segmental loss of myelin and in some instances, evidence of remyelination. Clinically, patients with demyelinating neuropathy can be seen with inherited disorders (Charcot-Marie-Tooth disease) or acquired disorders, typically immune-mediated or inflammatory. The acquired disorders can be either acute or subacute as seen in the acute inflammatory demyelinating polyneuropathy (AIDP) form of Guillain-Barré syndrome or chronic progressive or relapsing disorders such as chronic inflammatory demyelinating polyneuropathy. It is important to develop a logical approach to diagnosing these disorders. This requires an understanding of the clinical, genetic, physiological, and pathological features of these neuropathies. Clinically, important features to consider are the temporal progression, degree of symmetry, and involvement of proximal as well as distal muscles. Genetically, recognizing the different inheritance patterns and age of onset allow for a coordinated approach to determining a specific genotype. Physiologically, besides nerve conduction slowing, other physiological hallmarks of demyelination include temporal dispersion of compound motor action potentials (CMAP) on proximal stimulation, conduction block, and distal CMAP duration prolongation with certain patterns of involvement pointing to specific disorders. This chapter focuses on these various aspects of the evaluation of patients with chronic acquired demyelinating neuropathies to develop a comprehensive and thoughtful diagnostic concept. Copyright © 2013 Elsevier B.V. All rights reserved.

Remodeling of motor units after nerve regeneration studied by quantitative electromyography.

PubMed

Krarup, Christian; Boeckstyns, Michel; Ibsen, Allan; Moldovan, Mihai; Archibald, Simon

2016-02-01

Peripheral nerve has the capacity to regenerate after nerve lesions; during reinnervation of muscle motor units are gradually reestablished. The aim of this study was to follow the time course of reestablishing and remodeling of motor units in relation to recovery of force after different types of nerve repair. Reinnervation of muscle was compared clinically and electrophysiologically in complete median or ulnar nerve lesions with short gap lengths in the distal forearm repaired with a collagen nerve conduit (11 nerves) or nerve suture (10 nerves). Reestablishment of motor units was studied by quantitative EMG and recording of evoked compound muscle action potential (CMAP) during a 24-month observation period after nerve repair. Force recovered partially to about 80% of normal. Denervation activity gradually decreased during reinnervation though it was still increased at 24 months. Nascent motor unit potentials (MUPs) at early reinnervation were prolonged and polyphasic. During longitudinal studies, MUPs remained prolonged and their amplitudes gradually increased markedly. Firing of MUPs was unstable throughout the study. CMAPs gradually increased and the number of motor units recovered to approximately 20% of normal. There was weak evidence of CMAP amplitude recovery after suture ahead of conduit repair but without treatment related differences at 2 years. Surgical repair of nerve lesions with a nerve conduit or suture supported recovery of force and of motor unit reinnervation to the same extent. Changes occurred at a higher rate during early regeneration and slower after 12 months but should be followed for at least 2 years to assess outcome. EMG changes reflected extensive remodeling of motor units from early nascent units to a mature state with greatly enlarged units due to axonal regeneration and collateral sprouting and maturation of regenerated nerve and reinnervated muscle fibers after both types of repair. Remodeling of motor units after peripheral nerve lesions provides the basis for better recovery of force than the number of motor axons and units. There were no differences after repair with a collagen nerve conduit and nerve suture at short nerve gap lengths. The reduced number of motor units indicates that further improvement of repair procedures and nerve environment is needed. Copyright © 2015 International Federation of Clinical Neurophysiology. Published by Elsevier Ireland Ltd. All rights reserved.

Exploring the molecular mechanisms of Traditional Chinese Medicine components using gene expression signatures and connectivity map.

PubMed

Yoo, Minjae; Shin, Jimin; Kim, Hyunmin; Kim, Jihye; Kang, Jaewoo; Tan, Aik Choon

2018-04-04

Traditional Chinese Medicine (TCM) has been practiced over thousands of years in China and other Asian countries for treating various symptoms and diseases. However, the underlying molecular mechanisms of TCM are poorly understood, partly due to the "multi-component, multi-target" nature of TCM. To uncover the molecular mechanisms of TCM, we perform comprehensive gene expression analysis using connectivity map. We interrogated gene expression signatures obtained 102 TCM components using the next generation Connectivity Map (CMap) resource. We performed systematic data mining and analysis on the mechanism of action (MoA) of these TCM components based on the CMap results. We clustered the 102 TCM components into four groups based on their MoAs using next generation CMap resource. We performed gene set enrichment analysis on these components to provide additional supports for explaining these molecular mechanisms. We also provided literature evidence to validate the MoAs identified through this bioinformatics analysis. Finally, we developed the Traditional Chinese Medicine Drug Repurposing Hub (TCM Hub) - a connectivity map resource to facilitate the elucidation of TCM MoA for drug repurposing research. TCMHub is freely available in http://tanlab.ucdenver.edu/TCMHub. Molecular mechanisms of TCM could be uncovered by using gene expression signatures and connectivity map. Through this analysis, we identified many of the TCM components possess diverse MoAs, this may explain the applications of TCM in treating various symptoms and diseases. Copyright © 2018 The Authors. Published by Elsevier B.V. All rights reserved.

Zika virus-induced acute myelitis and motor deficits in adult interferon αβ/γ receptor knockout mice.

PubMed

Zukor, Katherine; Wang, Hong; Siddharthan, Venkatraman; Julander, Justin G; Morrey, John D

2018-06-01

Zika virus (ZIKV) has received widespread attention because of its effect on the developing fetus. It is becoming apparent, however, that severe neurological sequelae, such as Guillian-Barrë syndrome (GBS), myelitis, encephalitis, and seizures can occur after infection of adults. This study demonstrates that a contemporary strain of ZIKV can widely infect astrocytes and neurons in the brain and spinal cord of adult, interferon α/β receptor knockout mice (AG129 strain) and cause progressive hindlimb paralysis, as well as severe seizure-like activity during the acute phase of disease. The severity of hindlimb motor deficits correlated with increased numbers of ZIKV-infected lumbosacral spinal motor neurons and decreased numbers of spinal motor neurons. Electrophysiological compound muscle action potential (CMAP) amplitudes in response to stimulation of the lumbosacral spinal cord were reduced when obvious motor deficits were present. ZIKV immunoreactivity was high, intense, and obvious in tissue sections of the brain and spinal cord. Infection in the brain and spinal cord was also associated with astrogliosis as well as T cell and neutrophil infiltration. CMAP and histological analysis indicated that peripheral nerve and muscle functions were intact. Consequently, motor deficits in these circumstances appear to be primarily due to myelitis and possibly encephalitis as opposed to a peripheral neuropathy or a GBS-like syndrome. Thus, acute ZIKV infection of adult AG129 mice may be a useful model for ZIKV-induced myelitis, encephalitis, and seizure activity.

Palpebral portion of the orbicularis oculi muscle to repetitive nerve stimulation testing: A potential assessment indicator in patients with generalized myasthenia gravis.

PubMed

Yan, Chong; Song, Jie; Pang, Song; Yi, Fangfang; Xi, Jianying; Zhou, Lei; Ding, Ding; Wang, Weifeng; Qiao, Kai; Zhao, Chongbo

2018-02-01

Repetitive nerve stimulation (RNS) is a valuable diagnostic method for myasthenia gravis (MG). However, its association with clinical severity was scarcely studied. We reviewed medical records and retrospectively enrolled 121 generalized MG patients. Sensitivity of different muscles to RNS and clinical scoring systems was evaluated. RNS testing revealed facial muscles have the highest positive rate, followed by proximal muscles and distal muscles, with the palpebral portion of the orbicularis oculi muscle most sensitive. Amplitude decrement of compound muscle action potential (CMAP) in the palpebral portion of the orbicularis oculi muscle is related to quantitative myasthenia gravis (QMG) scores, MG-specific manual muscle testing (MMT) scores and myasthenia gravis-related activities of daily living (MG-ADL) scores. We suggest that RNS testing of the palpebral portion of the orbicularis oculi muscle is a potential assessment indicator in patients with generalized MG. Copyright © 2017 Elsevier Ltd. All rights reserved.

Electrodiagnostic studies in presumptive primary hypothyroidism and polyneuropathy in dogs with reevaluation during hormone replacement therapy.

PubMed

Giza, Elżbieta Gabriela; Płonek, Marta; Nicpoń, Józef Marian; Wrzosek, Marcin Adam

2016-05-21

Peripheral neuropathy is the most common neurological manifestation of canine hypothyroidism. Data concerning electrodiagnostic studies in hypothyroid associated polyneuropathy in dogs are very limited and usually lack a reevaluation after hormone replacement therapy. The objective of this study was to perform a detailed, retrospective analysis of electromyographic (EMG), motor nerve conduction velocity (MNCV), F-wave and brainstem auditory evoked response (BAER) findings in 24 dogs with presumptive primary hypothyroidism and polyneuropathy with a comparison of the results before and after initiation of levothyroxine treatment with the assessment of the clinical outcome. The results obtained from hypothyroid dogs showed a significant reduction in MNCV at a proximal-distal and middle-distal stimulation, decreased amplitudes of compound muscle action potentials (CMAP), an increased CMAP duration and a prolonged distal latency prior to treatment. Fifty percent of the dogs had an increased F-wave latency. A normal BAER recording was found in 78 % of the hypothyroid patients without vestibular impairment. Bilaterally increased peak V latencies and increased interpeak I-V latencies were found in the remaining individuals. Dogs with concurrent vestibular impairment had ipsilaterally increased peak latencies with normal interpeak latencies and decreased amplitudes of wave I and II. A comparison of the findings before and after 2 months of treatment revealed a decrease in the pathological activity on EMG, an improvement of proximal, middle and distal CMAP amplitudes and an increase in the proximal-distal conduction velocity in all dogs. F-wave latency improved in 38 % of dogs. The BAER reexamination revealed a persistent prolongation of peak I, II, III and V latencies and decreased wave I amplitude on the affected side in all dogs manifesting vestibular signs. Conversely, in dogs without vestibular signs, the peak V and interpeak I-V latencies decreased to normal values after a given time of the treatment. The results indicate a demyelinating and axonal pattern of polyneuropathy in dogs with suspected hypothyroidism. Most of the patients without vestibular signs showed neither peripheral nor central auditory pathway impairment, concurrent to the generalized neuropathy. The follow-up examination showed a very good clinical outcome and only partial improvement in electrophysiological assessment.

Brief psychological intervention after self-harm: randomised controlled trial from Pakistan.

PubMed

Husain, Nusrat; Afsar, Salahuddin; Ara, Jamal; Fayyaz, Hina; Rahman, Raza Ur; Tomenson, Barbara; Hamirani, Munir; Chaudhry, Nasim; Fatima, Batool; Husain, Meher; Naeem, Farooq; Chaudhry, Imran B

2014-06-01

Self-harm is a major risk factor for completed suicide. To determine the efficacy of a brief psychological intervention - culturally adapted manual-assisted problem-solving training (C-MAP) - delivered following an episode of self-harm compared with treatment as usual (TAU). The study was a randomised controlled assessor-masked clinical trial (trial registration: ClinicalTrials.gov NCT01308151). All patients admitted after an episode of self-harm during the previous 7 days to the participating medical units of three university hospitals in Karachi, Pakistan, were included in the study. A total of 250 patients were screened and 221 were randomly allocated to C-MAP plus treatment as usual (TAU) or to TAU alone. All patients were assessed at baseline, at 3 months (end of intervention) and at 6 months after baseline. The primary outcome measure was reduction in suicidal ideation at 3 months. The secondary outcome measures included hopelessness, depression, coping resources and healthcare utilisation. A total of 108 patients were randomised to the C-MAP group and 113 to the TAU group. Patients in the C-MAP group showed statistically significant improvement on the Beck Scale for Suicide Ideation and Beck Hopelessness Inventory, which was sustained at 3 months after the completion of C-MAP. There was also a significant reduction in symptoms of depression compared with patients receiving TAU. The positive outcomes of this brief psychological intervention in patients attempting self-harm are promising and suggest that C-MAP may have a role in suicide prevention. Royal College of Psychiatrists.

Neuregulin Facilitates Nerve Regeneration by Speeding Schwann Cell Migration via ErbB2/3-Dependent FAK Pathway

PubMed Central

Chang, Hung-Ming; Shyu, Ming-Kwang; Tseng, Guo-Fang; Liu, Chiung-Hui; Chang, Hung-Shuo; Lan, Chyn-Tair; Hsu, Wen-Ming; Liao, Wen-Chieh

2013-01-01

Background Adequate migration of Schwann cells (Sc) is crucial for axon-guidance in the regenerative process after peripheral nerve injury (PNI). Considering neuregulin-erbB-FAK signaling is an essential pathway participating in the regulation of Sc migration during development, the present study is aimed to examine whether neuregulin would exert its beneficial effects on adult following PNI and further determine the potential changes of downstream pathway engaged in neuro-regeneration by both in vitro and in vivo approaches. Methodology and Principal Findings Cultured RSC96 cells treated with neuregulin were processed for erbB2/3 immunofluorescence and FAK immunoblotings. The potential effects of neuregulin on Sc were assessed by cell adherence, spreading, and migration assays. In order to evaluate the functional significance of neuregulin on neuro-regeneration, the in vivo model of PNI was performed by chronic end-to-side neurorrhaphy (ESN). In vitro studies indicated that after neuregulin incubation, erbB2/3 were not only expressed in cell membranes, but also distributed throughout the cytoplasm and nucleus of RSC96 cells. Activation of erbB2/3 was positively correlated with FAK phosphorylation. Neuregulin also increases Sc adherence, spreading, and migration by 127.2±5.0%, 336.8±3.0%, and 80.0±5.7%, respectively. As for in vivo study, neuregulin significantly accelerates the speed of Sc migration and increases Sc expression in the distal stump of injured nerves. Retrograde labeling and compound muscle action potential recordings (CMAP) also showed that neuregulin successfully facilitates nerve regeneration by eliciting noticeably larger CMAP and promoting quick re-innervation of target muscles. Conclusions As neuregulin successfully improves axo-glial interaction by speeding Sc migration via the erbB2/3-FAK pathway, therapeutic use of neuregulin may thus serve as a promising strategy to facilitate the progress of nerve regeneration after PNI. PMID:23301073

Best time window for the use of calcium-modulating agents to improve functional recovery in injured peripheral nerves-An experiment in rats.

PubMed

Yan, Yuhui; Shen, Feng-Yi; Agresti, Michael; Zhang, Lin-Ling; Matloub, Hani S; LoGiudice, John A; Havlik, Robert; Li, Jifeng; Gu, Yu-Dong; Yan, Ji-Geng

2017-09-01

Peripheral nerve injury can have a devastating effect on daily life. Calcium concentrations in nerve fibers drastically increase after nerve injury, and this activates downstream processes leading to neuron death. Our previous studies showed that calcium-modulating agents decrease calcium accumulation, which aids in regeneration of injured peripheral nerves; however, the optimal therapeutic window for this application has not yet been identified. In this study, we show that calcium clearance after nerve injury is positively correlated with functional recovery in rats suffering from a crushed sciatic nerve injury. After the nerve injury, calcium accumulation increased. Peak volume is from 2 to 8 weeks post injury; calcium accumulation then gradually decreased over the following 24-week period. The compound muscle action potential (CMAP) measurement from the extensor digitorum longus muscle recovered to nearly normal levels in 24 weeks. Simultaneously, real-time polymerase chain reaction results showed that upregulation of calcium-ATPase (a membrane protein that transports calcium out of nerve fibers) mRNA peaked at 12 weeks. These results suggest that without intervention, the peak in calcium-ATPase mRNA expression in the injured nerve occurs after the peak in calcium accumulation, and CMAP recovery continues beyond 24 weeks. Immediately using calcium-modulating agents after crushed nerve injury improved functional recovery. These studies suggest that a crucial time frame in which to initiate effective clinical approaches to accelerate calcium clearance and nerve regeneration would be prior to 2 weeks post injury. © 2017 Wiley Periodicals, Inc. © 2017 Wiley Periodicals, Inc.

Comparison of Transcranial Magnetic Stimulation and Electroneuronography Between Bell's Palsy and Ramsay Hunt Syndrome in Their Acute Stages

PubMed Central

Hur, Dong Min; Lee, Young Hee; Kim, Sung Hoon; Park, Jung Mi; Kim, Ji Hyun; Yong, Sang Yeol; Shinn, Jong Mock; Oh, Kyung Joon

2013-01-01

Objective To examine the neurophysiologic status in patients with idiopathic facial nerve palsy (Bell's palsy) and Ramsay Hunt syndrome (herpes zoster oticus) within 7 days from onset of symptoms, by comparing the amplitude of compound muscle action potentials (CMAP) of facial muscles in electroneuronography (ENoG) and transcranial magnetic stimulation (TMS). Methods The facial nerve conduction study using ENoG and TMS was performed in 42 patients with Bell's palsy and 14 patients with Ramsay Hunt syndrome within 7 days from onset of symptoms. Denervation ratio was calculated as CMAP amplitude evoked by ENoG or TMS on the affected side as percentage of the amplitudes on the healthy side. The severity of the facial palsy was graded according to House-Brackmann facial grading scale (H-B FGS). Results In all subjects, the denervation ratio in TMS (71.53±18.38%) was significantly greater than the denervation ratio in ENoG (41.95±21.59%). The difference of denervation ratio between ENoG and TMS was significantly smaller in patients with Ramsay Hunt syndrome than in patients with Bell's palsy. The denervation ratio of ENoG or TMS did not correlated significantly with the H-B FGS. Conclusion In the electrophysiologic study for evaluation in patients with facial palsy within 7 days from onset of symptoms, ENoG and TMS are useful in gaining additional information about the neurophysiologic status of the facial nerve and may help to evaluate prognosis and set management plan. PMID:23525840

Inter- and intrapatient variability of facial nerve response areas in the floor of the fourth ventricle.

PubMed

Bertalanffy, Helmut; Tissira, Nadir; Krayenbühl, Niklaus; Bozinov, Oliver; Sarnthein, Johannes

2011-03-01

Surgical exposure of intrinsic brainstem lesions through the floor of the 4th ventricle requires precise identification of facial nerve (CN VII) fibers to avoid damage. To assess the shape, size, and variability of the area where the facial nerve can be stimulated electrophysiologically on the surface of the rhomboid fossa. Over a period of 18 months, 20 patients were operated on for various brainstem and/or cerebellar lesions. Facial nerve fibers were stimulated to yield compound muscle action potentials (CMAP) in the target muscles. Using the sites of CMAP yield, a detailed functional map of the rhomboid fossa was constructed for each patient. Lesions resected included 14 gliomas, 5 cavernomas, and 1 epidermoid cyst. Of 40 response areas mapped, 19 reached the median sulcus. The distance from the obex to the caudal border of the response area ranged from 8 to 27 mm (median, 17 mm). The rostrocaudal length of the response area ranged from 2 to 15 mm (median, 5 mm). Facial nerve response areas showed large variability in size and position, even in patients with significant distance between the facial colliculus and underlying pathological lesion. Lesions located close to the facial colliculus markedly distorted the response area. This is the first documentation of variability in the CN VII response area in the rhomboid fossa. Knowledge of this remarkable variability may facilitate the assessment of safe entry zones to the brainstem and may contribute to improved outcome following neurosurgical interventions within this sensitive area of the brain.

An in vivo study of tricalcium phosphate and glutaraldehyde crosslinking gelatin conduits in peripheral nerve repair.

PubMed

Chen, Ming-Hong; Chen, Pei-Ru; Chen, Mei-Hsiu; Hsieh, Sung-Tsang; Huang, Jing-Shan; Lin, Feng-Huei

2006-04-01

In order to modulate the mechanical properties of gelatin, we previously developed a biodegradable composite composed by tricalcium phosphate and glutaraldehyde crosslinking gelatin (GTG) feasible for surgical manipulation. In this study, we evaluated the in vivo applications of GTG conduit for peripheral nerve repair. The effect of sciatic nerve reconstruction was compared between resorbable permeable GTG conduits and durable impermeable silicone tubes. Traditional methods of assessing nerve recovery following peripheral nerve repair including histomorphometric and electrophysiologic features were conducted in our study. In addition, autotomy score and sciatic function index (SFI) in walking tract analysis were used as additional parameters for assessing the return of nerve function. Twenty-four weeks after sciatic nerve repair, the GTG conduits were harvested. Microscopically, regeneration of nerves was observed in the cross-section at the mid portion of all implanted GTG conduits. The cross-sectional area of regenerated nerve of the GTG group was significant larger than that of the silicone group. In the compound muscle action potentials (CMAP), the mean recovery index of CMAP amplitude was 0.24 +/- 0.02 for the silicone group, 0.41 +/- 0.07 for the GTG group. The mean SFI increased with time in the GTG group during the evaluation period until 24 weeks. Walking tract analysis showed a higher SFI score in the GTG group at both 12 and 24 weeks. The difference reached a significant level at 24 weeks. Thus, the histomorphometric, electrophysiologic, and functional assessments demonstrate that GTG can be a candidate for peripheral nerve repair.

Nonparametric Trajectory Analysis of CMAPS Data

EPA Science Inventory

As part of the Cleveland Multiple Air Pollutant Study (CMAPS), 30-minute average concentrations of the elemental composition of PM2.5 were made at two sites during the months of August 2009 and February 2010. The elements measured were: Al, As, Ba, Be, Ca, Cd, Ce, Co, Cr, Cs, Cu...

Long Dynamics Simulations of Proteins Using Atomistic Force Fields and a Continuum Representation of Solvent Effects: Calculation of Structural and Dynamic Properties

PubMed Central

Li, Xianfeng; Hassan, Sergio A.; Mehler, Ernest L.

2006-01-01

Long dynamics simulations were carried out on the B1 immunoglobulin-binding domain of streptococcal protein G (ProtG) and bovine pancreatic trypsin inhibitor (BPTI) using atomistic descriptions of the proteins and a continuum representation of solvent effects. To mimic frictional and random collision effects, Langevin dynamics (LD) were used. The main goal of the calculations was to explore the stability of tens-of-nanosecond trajectories as generated by this molecular mechanics approximation and to analyze in detail structural and dynamical properties. Conformational fluctuations, order parameters, cross correlation matrices, residue solvent accessibilities, pKa values of titratable groups, and hydrogen-bonding (HB) patterns were calculated from all of the trajectories and compared with available experimental data. The simulations comprised over 40 ns per trajectory for ProtG and over 30 ns per trajectory for BPTI. For comparison, explicit water molecular dynamics simulations (EW/MD) of 3 ns and 4 ns, respectively, were also carried out. Two continuum simulations were performed on each protein using the CHARMM program, one with the all-atom PAR22 representation of the protein force field (here referred to as PAR22/LD simulations) and the other with the modifications introduced by the recently developed CMAP potential (CMAP/LD simulations). The explicit solvent simulations were performed with PAR22 only. Solvent effects are described by a continuum model based on screened Coulomb potentials (SCP) reported earlier, i.e., the SCP-based implicit solvent model (SCP–ISM). For ProtG, both the PAR22/LD and the CMAP/LD 40-ns trajectories were stable, yielding Cα root mean square deviations (RMSD) of about 1.0 and 0.8 Å respectively along the entire simulation time, compared to 0.8 Å for the EW/MD simulation. For BPTI, only the CMAP/LD trajectory was stable for the entire 30-ns simulation, with a Cα RMSD of ≈ 1.4 Å, while the PAR22/LD trajectory became unstable early in the simulation, reaching a Cα RMSD of about 2.7 Å and remaining at this value until the end of the simulation; the Cα RMSD of the EW/MD simulation was about 1.5 Å. The source of the instabilities of the BPTI trajectories in the PAR22/LD simulations was explored by an analysis of the backbone torsion angles. To further validate the findings from this analysis of BPTI, a 35-ns SCP–ISM simulation of Ubiquitin (Ubq) was carried out. For this protein, the CMAP/LD simulation was stable for the entire simulation time (Cα RMSD of ≈1.0 Å), while the PAR22/LD trajectory showed a trend similar to that in BPTI, reaching a Cα RMSD of ≈1.5 Å at 7 ns. All the calculated properties were found to be in agreement with the corresponding experimental values, although local deviations were also observed. HB patterns were also well reproduced by all the continuum solvent simulations with the exception of solvent-exposed side chain–side chain (sc–sc) HB in ProtG, where several of the HB interactions observed in the crystal structure and in the EW/MD simulation were lost. The overall analysis reported in this work suggests that the combination of an atomistic representation of a protein with a CMAP/CHARMM force field and a continuum representation of solvent effects such as the SCP–ISM provides a good description of structural and dynamic properties obtained from long computer simulations. Although the SCP–ISM simulations (CMAP/LD) reported here were shown to be stable and the properties well reproduced, further refinement is needed to attain a level of accuracy suitable for more challenging biological applications, particularly the study of protein–protein interactions. PMID:15959866

R-CMap-An open-source software for concept mapping.

PubMed

Bar, Haim; Mentch, Lucas

2017-02-01

Planning and evaluating projects often involves input from many stakeholders. Fusing and organizing many different ideas, opinions, and interpretations into a coherent and acceptable plan or project evaluation is challenging. This is especially true when seeking contributions from a large number of participants, especially when not all can participate in group discussions, or when some prefer to contribute their perspectives anonymously. One of the major breakthroughs in the area of evaluation and program planning has been the use of graphical tools to represent the brainstorming process. This provides a quantitative framework for organizing ideas and general concepts into simple-to-interpret graphs. We developed a new, open-source concept mapping software called R-CMap, which is implemented in R. This software provides a graphical user interface to guide users through the analytical process of concept mapping. The R-CMap software allows users to generate a variety of plots, including cluster maps, point rating and cluster rating maps, as well as pattern matching and go-zone plots. Additionally, R-CMap is capable of generating detailed reports that contain useful statistical summaries of the data. The plots and reports can be embedded in Microsoft Office tools such as Word and PowerPoint, where users may manually adjust various plot and table features to achieve the best visual results in their presentations and official reports. The graphical user interface of R-CMap allows users to define cluster names, change the number of clusters, select rating variables for relevant plots, and importantly, select subsets of respondents by demographic criteria. The latter is particularly useful to project managers in order to identify different patterns of preferences by subpopulations. R-CMap is user-friendly, and does not require any programming experience. However, proficient R users can add to its functionality by directly accessing built-in functions in R and sharing new features with the concept mapping community. Copyright © 2016 Elsevier Ltd. All rights reserved.

Systematic drug safety evaluation based on public genomic expression (Connectivity Map) data: Myocardial and infectious adverse reactions as application cases

DOE Office of Scientific and Technical Information (OSTI.GOV)

Wang, Kejian, E-mail: kejian.wang.bio@gmail.com; Weng, Zuquan; Sun, Liya

Adverse drug reaction (ADR) is of great importance to both regulatory agencies and the pharmaceutical industry. Various techniques, such as quantitative structure–activity relationship (QSAR) and animal toxicology, are widely used to identify potential risks during the preclinical stage of drug development. Despite these efforts, drugs with safety liabilities can still pass through safety checkpoints and enter the market. This situation raises the concern that conventional chemical structure analysis and phenotypic screening are not sufficient to avoid all clinical adverse events. Genomic expression data following in vitro drug treatments characterize drug actions and thus have become widely used in drug repositioning. Inmore » the present study, we explored prediction of ADRs based on the drug-induced gene-expression profiles from cultured human cells in the Connectivity Map (CMap) database. The results showed that drugs inducing comparable ADRs generally lead to similar CMap expression profiles. Based on such ADR-gene expression association, we established prediction models for various ADRs, including severe myocardial and infectious events. Drugs with FDA boxed warnings of safety liability were effectively identified. We therefore suggest that drug-induced gene expression change, in combination with effective computational methods, may provide a new dimension of information to facilitate systematic drug safety evaluation. - Highlights: • Drugs causing common toxicity lead to similar in vitro gene expression changes. • We built a model to predict drug toxicity with drug-specific expression profiles. • Drugs with FDA black box warnings were effectively identified by our model. • In vitro assay can detect severe toxicity in the early stage of drug development.« less

Pathophysiologic insights into motor axonal function in Kennedy disease.

PubMed

Vucic, Steve; Kiernan, Matthew C

2007-11-06

Kennedy disease (KD), or spinobulbomuscular atrophy, is a slowly progressive inherited neurodegenerative disorder, marked by prominent fasciculations that typically precede the development of other symptoms. Although the genetic basis of KD relates to triplet (CAG) repeat expansion in the androgen receptor (AR) gene on the X chromosome, the mechanisms underlying the clinical presentation in KD have yet to be established. Consequently, the present study applied axonal excitability techniques to investigate the pathophysiologic mechanisms associated with KD. Peripheral nerve excitability studies were undertaken in 7 patients with KD with compound muscle action potentials (CMAP) recorded from the right abductor pollicis brevis. Strength-duration time constant (KD 0.54 +/- 0.03 msec; controls, 0.41 +/- 0.02 msec, p < 0.01) and the hyperpolarizing current/threshold gradient (KD 0.42 +/- 0.01; controls, 0.37 +/- 0.01, p < 0.05) were significantly increased in KD. Strength-duration time constant correlated with the CMAP amplitude (R = 0.68) and the fasciculation frequency (R = 0.62). Threshold electrotonus revealed greater changes in response to subthreshold depolarizing (KD TEd [90 to 100 msec], 50.75 +/- 1.98%; controls TEd [90 to 100 msec], 45.67 +/- 0.67%, p < 0.01) and hyperpolarizing (KD TEh [90 to 100 msec], 128.5 +/- 6.9%; controls TEh [90 to 100 msec], 120.5 +/- 2.4%) conditioning pulses. Measurements of refractoriness, superexcitability, and late subexcitability changed appropriately for axonal hyperpolarization, perhaps reflecting the effects of increased ectopic activity. In total, the increase in the strength-duration time constant may be the primary event, occurring early in course of the disease, contributing to the development of axonal hyperexcitability in Kennedy disease, and thereby to the generation of fasciculations, a characteristic hallmark of the disease.

Modularity, quaternion-Kähler spaces, and mirror symmetry

DOE Office of Scientific and Technical Information (OSTI.GOV)

Alexandrov, Sergei; Banerjee, Sibasish

2013-10-15

We provide an explicit twistorial construction of quaternion-Kähler manifolds obtained by deformation of c-map spaces and carrying an isometric action of the modular group SL(2,Z). The deformation is not assumed to preserve any continuous isometry and therefore this construction presents a general framework for describing NS5-brane instanton effects in string compactifications with N= 2 supersymmetry. In this context the modular invariant parametrization of twistor lines found in this work yields the complete non-perturbative mirror map between type IIA and type IIB physical fields.

Neighbourhood Analysis to Foster Meaningful Learning Using Concept Mapping in Science Education

ERIC Educational Resources Information Center

Correia, P. R. M.; Cicuto, C. A. T.

2014-01-01

One critical aspect that hinders the systematic use of concept mapping in everyday classrooms is the difficulty of providing high-quality feedback to students so as to keep improving and revising their concept maps (Cmaps). The development of an innovative way to analyse, at a glance, students' Cmaps is presented to allow a diagnostic assessment…

Using Concept Maps as Instructional Materials to Foster the Understanding of the Atomic Model and Matter-Energy Interaction

ERIC Educational Resources Information Center

Aguiar, Joana G.; Correia, Paulo R. M.

2016-01-01

In this paper, we explore the use of concept maps (Cmaps) as instructional materials prepared by teachers, to foster the understanding of chemistry. We choose fireworks as a macroscopic event to teach basic chemical principles related to the Bohr atomic model and matter-energy interaction. During teachers' Cmap navigation, students can experience…

The IHMC CmapTools software in research and education: a multi-level use case in Space Meteorology

NASA Astrophysics Data System (ADS)

Messerotti, Mauro

2010-05-01

The IHMC (Institute for Human and Machine Cognition, Florida University System, USA) CmapTools software is a powerful multi-platform tool for knowledge modelling in graphical form based on concept maps. In this work we present its application for the high-level development of a set of multi-level concept maps in the framework of Space Meteorology to act as the kernel of a space meteorology domain ontology. This is an example of a research use case, as a domain ontology coded in machine-readable form via e.g. OWL (Web Ontology Language) is suitable to be an active layer of any knowledge management system embedded in a Virtual Observatory (VO). Apart from being manageable at machine level, concept maps developed via CmapTools are intrinsically human-readable and can embed hyperlinks and objects of many kinds. Therefore they are suitable to be published on the web: the coded knowledge can be exploited for educational purposes by the students and the public, as the level of information can be naturally organized among linked concept maps in progressively increasing complexity levels. Hence CmapTools and its advanced version COE (Concept-map Ontology Editor) represent effective and user-friendly software tools for high-level knowledge represention in research and education.

Functional recovery of completely denervated muscle: implications for innervation of tissue-engineered muscle.

PubMed

Kang, Sung-Bum; Olson, Jennifer L; Atala, Anthony; Yoo, James J

2012-09-01

Tissue-engineered muscle has been proposed as a solution to repair volumetric muscle defects and to restore muscle function. To achieve functional recovery, engineered muscle tissue requires integration of the host nerve. In this study, we investigated whether denervated muscle, which is analogous to tissue-engineered muscle tissue, can be reinnervated and can recover muscle function using an in vivo model of denervation followed by neurotization. The outcomes of this investigation may provide insights on the ability of tissue-engineered muscle to integrate with the host nerve and acquire normal muscle function. Eighty Lewis rats were classified into three groups: a normal control group (n=16); a denervated group in which sciatic innervations to the gastrocnemius muscle were disrupted (n=32); and a transplantation group in which the denervated gastrocnemius was repaired with a common peroneal nerve graft into the muscle (n=32). Neurofunctional behavior, including extensor postural thrust (EPT), withdrawal reflex latency (WRL), and compound muscle action potential (CMAP), as well as histological evaluations using alpha-bungarotoxin and anti-NF-200 were performed at 2, 4, 8, and 12 weeks (n=8) after surgery. We found that EPT was improved by transplantation of the nerve grafts, but the EPT values in the transplanted animals at 12 weeks postsurgery were still significantly lower than those measured for the normal control group at 4 weeks (EPT, 155.0±38.9 vs. 26.3±13.8 g, p<0.001; WRL, 2.7±2.30 vs. 8.3±5.5 s, p=0.027). In addition, CMAP latency and amplitude significantly improved with time after surgery in the transplantation group (p<0.001, one-way analysis of variance), and at 12 weeks postsurgery, CMAP latency and amplitude were not statistically different from normal control values (latency, 0.9±0.0 vs. 1.3±0.7 ms, p=0.164; amplitude, 30.2±7.0 vs. 46.4±26.9 mV, p=0.184). Histologically, regeneration of neuromuscular junctions was seen in the transplantation group. This study indicates that transplanted nerve tissue is able to regenerate neuromuscular junctions within denervated muscle, and thus the muscle can recover partial function. However, the function of the denervated muscle remains in the subnormal range even at 12 weeks after direct nerve transplantation. These results suggest that tissue-engineered muscle, which is similarly denervated, could be innervated and become functional in vivo if it is properly integrated with the host nerve.

Use of the SF-8 to assess health-related quality of life for a chronically ill, low-income population participating in the Central Louisiana Medication Access Program (CMAP).

PubMed

Lefante, John J; Harmon, Gary N; Ashby, Keith M; Barnard, David; Webber, Larry S

2005-04-01

The utility of the SF-8 for assessing health-related quality of life (HRQL) is demonstrated. Race and gender differences in physical component (PCS) and mental component (MCS) summary scores among participants in the CENLA Medication Access Program (CMAP), along with comparisons to the United States population are made. Age-adjusted multiple linear regression analyses were used to compare 1687 CMAP participants to the US population. Internal race and gender comparisons, adjusting for age and the number of self reported diagnoses, were also obtained. The paired t-test was used to assess 6-month change in PCS and MCS scores for a subset of 342 participants. CMAP participants have PCS and MCS scores that are significantly 10-12 points lower than the US population, indicating lower self-reported HRQL. Females have significantly higher PCS and significantly lower MCS than males. African-Americans have significantly higher MCS than Caucasians. Significant increases in both PCS and MCS were observed for the subset of participants after 6 months of intervention. The expected lower baseline PCS and MCS measures and the expected associations with age and number of diagnoses indicate that the SF-8 survey is an effective tool for measuring the HRQL of participants in this program. Preliminary results indicate significant increases in both PCS and MCS 6 months after intervention.

Sea level static calibration of a compact multimission aircraft propulsion simulator with inlet flow distortion

NASA Technical Reports Server (NTRS)

Won, Mark J.

1990-01-01

Wind tunnel tests of propulsion-integrated aircraft models have identified inlet flow distortion as a major source of compressor airflow measurement error in turbine-powered propulsion simulators. Consequently, two Compact Multimission Aircraft Propulsion Simulator (CMAPS) units were statically tested at sea level ambient conditions to establish simulator operating performance characteristics and to calibrate the compressor airflow against an accurate bellmouth flowmeter in the presence of inlet flow distortions. The distortions were generated using various-shaped wire mesh screens placed upstream of the compressor. CMAPS operating maps and performance envelopes were obtained for inlet total pressure distortions (ratio of the difference between the maximum and minimum total pressures to the average total pressure) up to 35 percent, and were compared to baseline simulator operating characteristics for a uniform inlet. Deviations from CMAPS baseline performance were attributed to the coupled variation of both compressor inlet-flow distortion and Reynolds number index throughout the simulator operating envelope for each screen configuration. Four independent methods were used to determine CMAPS compressor airflow; direct compressor inlet and discharge measurements, an entering/exiting flow-balance relationships, and a correlation between the mixer pressure and the corrected compressor airflow. Of the four methods, the last yielded the least scatter in the compressor flow coefficient, approximately + or - 3 percent over the range of flow distortions.

Extending the golden hour: Partial resuscitative endovascular balloon occlusion of the aorta in a highly lethal swine liver injury model.

PubMed

Russo, Rachel M; Williams, Timothy K; Grayson, John Kevin; Lamb, Christopher M; Cannon, Jeremy W; Clement, Nathan F; Galante, Joseph M; Neff, Lucas P

2016-03-01

Combat-injured patients may require rapid and sustained support during transport; however, the prolonged aortic occlusion produced by conventional resuscitative endovascular balloon occlusion of the aorta (REBOA) may lead to substantial morbidity. Partial REBOA (P-REBOA) may permit longer periods of occlusion by allowing some degree of distal perfusion. However, the ability of this procedure to limit exsanguination is unclear. We evaluated the impact of P-REBOA on immediate survival and ongoing hemorrhage in a highly lethal swine liver injury model. Fifteen Yorkshire-cross swine were anesthetized, instrumented, splenectomized, and subjected to rapid 10% total blood loss followed by 30% liver amputation. Coagulopathy was created through colloid hemodilution. Randomized swine received no intervention (control), P-REBOA, or complete REBOA (C-REBOA). Central mean arterial pressure (cMAP), carotid blood flow, and blood loss were recorded. Balloons remained inflated in the P-REBOA and C-REBOA groups for 90 minutes followed by graded deflation. The study ended at 180 minutes from onset of hemorrhage or death of the animal. Survival analysis was performed, and data were analyzed using repeated-measures analysis of variance with post hoc pairwise comparisons. Mean survival times in the control, P-REBOA, and C-REBOA groups were, 25 ± 21, 86 ± 40, and 163 ± 20 minutes, respectively (p < 0.001). Blood loss was greater in the P-REBOA group than the C-REBOA or control groups, but this difference was not significant (4,722 ± 224, 3,834 ± 319, 3,818 ± 37 mL, respectively, p = 0.10). P-REBOA resulted in maintenance of near-baseline carotid blood flow and cMAP, while C-REBOA generated extreme cMAP and prolonged supraphysiologic carotid blood flow. Both experimental groups experienced profound decreases in cMAP following balloon deflation. In the setting of severe ongoing hemorrhage, P-REBOA increased survival time beyond the golden hour while maintaining cMAP and carotid flow at physiologic levels.

A list of tables summarizing various Cmap analysis, from which the final tables in the manuscript are based on

EPA Pesticide Factsheets

Various Cmap analyses within and across species and microarray platforms conducted and summarized to generate the tables in the publication.This dataset is associated with the following publication:Wang , R., A. Biales , N. Garcia-Reyero, E. Perkins, D. Villeneuve, G. Ankley, and D. Bencic. Fish Connectivity Mapping: Linking Chemical Stressors by Their MOA-Driven Transcriptomic Profiles. BMC Genomics. BioMed Central Ltd, London, UK, 17(84): 1-20, (2016).

Deficiency in Monocarboxylate Transporter 1 (MCT1) in Mice Delays Regeneration of Peripheral Nerves following Sciatic Nerve Crush

PubMed Central

Morrison, Brett M.; Tsingalia, Akivaga; Vidensky, Svetlana; Lee, Youngjin; Jin, Lin; Farah, Mohamed H.; Lengacher, Sylvain; Magistretti, Pierre J.; Pellerin, Luc; Rothstein, Jeffrey D.

2014-01-01

Peripheral nerve regeneration following injury occurs spontaneously, but many of the processes require metabolic energy. The mechanism of energy supply to axons has not previously been determined. In the central nervous system, monocarboxylate transporter 1 (MCT1), expressed in oligodendroglia, is critical for supplying lactate or other energy metabolites to axons. In the current study, MCT1 is shown to localize within the peripheral nervous system to perineurial cells, dorsal root ganglion neurons, and Schwann cells by MCT1 immunofluorescence and MCT1 tdTomato BAC reporter mice. To investigate whether MCT1 is necessary for peripheral nerve regeneration, sciatic nerves in MCT1 heterozygous null mice are crushed and peripheral nerve regeneration quantified electrophysiologically and anatomically. Compound muscle action potential (CMAP) recovery is delayed from a median of 21 days in wild-type mice to greater than 38 days in MCT1 heterozygote null mice. In fact, half of the MCT1 heterozygote null mice have no recovery of CMAP at 42 days, while all of the wild-type mice recovered. In addition, muscle fibers remain 40% more atrophic and neuromuscular junctions 40% more denervated at 42 days post-crush in the MCT1 heterozygote null mice than wild-type mice. The delay in nerve regeneration is not only in motor axons, as the number of regenerated axons in the sural sensory nerve of MCT1 heterozygote null mice at 4 weeks and tibial mixed sensory and motor nerve at 3 weeks is also significantly reduced compared to wild-type mice. This delay in regeneration may be partly through failed Schwann cell function, as there is reduced early phagocytosis of myelin debris and remyelination of axon segments. These data for the first time demonstrate that MCT1 is critical for regeneration of both sensory and motor axons in mice following sciatic nerve crush. PMID:25447940

Deficiency in monocarboxylate transporter 1 (MCT1) in mice delays regeneration of peripheral nerves following sciatic nerve crush.

PubMed

Morrison, Brett M; Tsingalia, Akivaga; Vidensky, Svetlana; Lee, Youngjin; Jin, Lin; Farah, Mohamed H; Lengacher, Sylvain; Magistretti, Pierre J; Pellerin, Luc; Rothstein, Jeffrey D

2015-01-01

Peripheral nerve regeneration following injury occurs spontaneously, but many of the processes require metabolic energy. The mechanism of energy supply to axons has not previously been determined. In the central nervous system, monocarboxylate transporter 1 (MCT1), expressed in oligodendroglia, is critical for supplying lactate or other energy metabolites to axons. In the current study, MCT1 is shown to localize within the peripheral nervous system to perineurial cells, dorsal root ganglion neurons, and Schwann cells by MCT1 immunofluorescence in wild-type mice and tdTomato fluorescence in MCT1 BAC reporter mice. To investigate whether MCT1 is necessary for peripheral nerve regeneration, sciatic nerves of MCT1 heterozygous null mice are crushed and peripheral nerve regeneration was quantified electrophysiologically and anatomically. Compound muscle action potential (CMAP) recovery is delayed from a median of 21 days in wild-type mice to greater than 38 days in MCT1 heterozygote null mice. In fact, half of the MCT1 heterozygote null mice have no recovery of CMAP at 42 days, while all of the wild-type mice recovered. In addition, muscle fibers remain 40% more atrophic and neuromuscular junctions 40% more denervated at 42 days post-crush in the MCT1 heterozygote null mice than wild-type mice. The delay in nerve regeneration is not only in motor axons, as the number of regenerated axons in the sural sensory nerve of MCT1 heterozygote null mice at 4 weeks and tibial mixed sensory and motor nerve at 3 weeks is also significantly reduced compared to wild-type mice. This delay in regeneration may be partly due to failed Schwann cell function, as there is reduced early phagocytosis of myelin debris and remyelination of axon segments. These data for the first time demonstrate that MCT1 is critical for regeneration of both sensory and motor axons in mice following sciatic nerve crush. Copyright © 2014 Elsevier Inc. All rights reserved.

Motor unit number index (MUNIX) derivation from the relationship between the area and power of surface electromyogram: a computer simulation and clinical study

NASA Astrophysics Data System (ADS)

Miralles, Francesc

2018-06-01

Objective. The motor unit number index (MUNIX) is a technique based on the surface electromyogram (sEMG) that is gaining acceptance as a method for monitoring motor neuron loss, because it is reliable and produces less discomfort than other electrodiagnostic techniques having the same intended purpose. MUNIX assumes that the relationship between the area of sEMG obtained at increasing levels of muscle activation and the values of a variable called ‘ideal case motor unit count’ (ICMUC), defined as the product of the ratio between area and power of the compound muscle action potential (CMAP) by that of the sEMG, is described by a decreasing power function. Nevertheless, the reason for this comportment is unknown. The objective of this work is to investigate if the definition of MUNIX could derive from more basic properties of the sEMG. Approach. The CMAP and sEMG epochs obtained at different levels of muscle activation from (1) the abductor pollicis brevis (APB) muscle of persons with and without a carpal tunnel syndrome (CTS) and (2) from a computer model of sEMG generation previously published were analysed. Main results. MUNIX reflects the power relationship existing between the area and power of a sEMG. The exponent of this function was smaller in patients with motor CTS than in the rest of the subjects. The analysis of the relationship between the area and power of a sEMG could aid in distinguishing a MUNIX reduction due to a motoneuron loss from that due to a loss of muscle fibre. Significance. MUNIX is derived from the relationship between the area and power of a sEMG. This relationship changes when there is a loss of motor units (MUs), which partially explains the diagnostic sensibility of MUNIX. Although the reasons for this change are unknown, it could reflect an increase in the proportion of MUs of great amplitude.

Neurophysiological criteria in the diagnosis of different clinical types of Guillain-Barre syndrome.

PubMed

Kalita, J; Misra, U K; Das, M

2008-03-01

The diagnostic yield of various neurophysiological criteria may vary in different subforms of Guillain-Barre syndrome (GBS), whose prevalence varies in different geographical areas. To evaluate the sensitivity of various neurophysiological criteria in different clinical subtypes of GBS, and their relationship with severity, duration and outcome. Consecutive patients with GBS underwent detailed clinical evaluation. Severity was graded on a scale from 0 to 10. Motor and sensory nerve conductions and F wave studies were performed. The diagnostic sensitivity of Albers et al (set 1), Cornblath (set 2), Ho et al (set 3), Dutch GBS study group (set 4), Italian GBS study group (set 5) and Albers and Kelly (set 6) criteria were evaluated and correlated with clinical subtypes of GBS, duration, severity and outcome. There were 51 patients. Mean disability was 6.8; 34 patients were bedridden and five needed a ventilator. Clinical presentation was pure motor in 31, motorsensory in 18 and pure sensory in two patients. The sensitivity of nerve conduction study in the diagnosis of GBS was highest in set 1 (88.2%) followed by set 3 (86.3%) and set 4 (82.4%) and lowest in set 2 (39.2%). The diagnostic yield of sets 1, 3 and 4 were also higher than sets 2, 5 and 6 in different clinical subtypes of GBS. As per Ho et al, patients could be categorised into acute inflammatory demyelinating polyradiculoneuropathy (44 (86.3%)), acute motor axonal neuropathy (4 (7.8%)) and acute motor sensory axonal neuropathy (3 (5.9%)). One (2%) patient died, 22.4% had complete, 57.1% partial and 18.4% poor recovery at 3 months. Outcome was related to severity of illness and compound muscle action potential (CMAP) amplitude. The sensitivity of different neurophysiological criteria in the diagnosis of Indian GBS patients varied from 39.2% to 88.2%. The outcome was related to severity of illness and CMAP amplitude.

The effect of polarized polychromatic noncoherent light (bioptron) therapy on patients with carpal tunnel syndrome.

PubMed

Raeissadat, Seyed Ahmad; Rayegani, Seyed Mansoor; Rezaei, Sajad; Sedighipour, Leyla; Bahrami, Mohammad Hasan; Eliaspour, Dariush; Karimzadeh, Afshin

2014-01-01

To study the effects of Polarized Polychromatic Noncoherent Light (Bioptron) therapy on patients with carpal tunnel syndrome (CTS). This study was designed as a randomized clinical trial. Forty four patients with mild or moderate CTS (confirmed by clinical and electrodiagnostic studies) were assigned randomly into two groups (intervention and control goups). At the beginning of the study, both groups received wrist splinting for 8 weeks. Bioptron light was applied for the intervention group (eight sessions, for 3/weeks). Bioptron was applied perpendicularly to the wrist from a 10 centimeter sdistance. Pain severity and electrodiagnostic measurements were compared from before to 8 weeks after initiating each treatment. Eight weeks after starting the treatments, the mean of pain severity based on Visual Analogue Scale (VAS) scores decreased significantly in both groups. Median Sensory Nerve Action Potential (SNAP) latency decreased significantly in both groups. However, other electrophysiological findings (median Compound Motor Action Potential (CMAP) latency and amplitude, also SNAP amplitude) did not change after the therapy in both groups. There was no meaningful difference between two groups regarding the changes in the pain severity. Bioptron with the above mentioned parameters led to therapeutic effects equal to splinting alone in patients with carpal tunnel syndrome. However, applying Bioptron with different therapeutic protocols and light parameters other than used in this study, perhaps longer duration of therapy and long term assessment may reveal different results favoring Bioptron therapy.

The Effect of Polarized Polychromatic Noncoherent Light (Bioptron) Therapy on Patients with Carpal Tunnel Syndrome

PubMed Central

Raeissadat, Seyed Ahmad; Rayegani, Seyed Mansoor; Rezaei, Sajad; Bahrami, Mohammad Hasan; Eliaspour, Dariush; Karimzadeh, Afshin

2014-01-01

Introduction: To study the effects of Polarized Polychromatic Noncoherent Light (Bioptron) therapy on patients with carpal tunnel syndrome (CTS). Methods: This study was designed as a randomized clinical trial. Forty four patients with mild or moderate CTS (confirmed by clinical and electrodiagnostic studies) were assigned randomly into two groups (intervention and control goups). At the beginning of the study, both groups received wrist splinting for 8 weeks. Bioptron light was applied for the intervention group (eight sessions, for 3/weeks). Bioptron was applied perpendicularly to the wrist from a 10 centimeter sdistance. Pain severity and electrodiagnostic measurements were compared from before to 8 weeks after initiating each treatment. Results: Eight weeks after starting the treatments, the mean of pain severity based on Visual Analogue Scale (VAS) scores decreased significantly in both groups. Median Sensory Nerve Action Potential (SNAP) latency decreased significantly in both groups. However, other electrophysiological findings (median Compound Motor Action Potential (CMAP) latency and amplitude, also SNAP amplitude) did not change after the therapy in both groups. There was no meaningful difference between two groups regarding the changes in the pain severity. Conclusion: Bioptron with the above mentioned parameters led to therapeutic effects equal to splinting alone in patients with carpal tunnel syndrome. However, applying Bioptron with different therapeutic protocols and light parameters other than used in this study, perhaps longer duration of therapy and long term assessment may reveal different results favoring Bioptron therapy. PMID:25606338

The impact of CmapTools utilization towards students' conceptual change on optics topic

NASA Astrophysics Data System (ADS)

Rofiuddin, Muhammad Rifqi; Feranie, Selly

2017-05-01

Science teachers need to help students identify their prior ideas and modify them based on scientific knowledge. This process is called as conceptual change. One of essential tools to analyze students' conceptual change is by using concept map. Concept Maps are graphical representations of knowledge that are comprised of concepts and the relationships between them. Constructing concept map is implemented by adapting the role of technology to support learning process, as it is suitable with Educational Ministry Regulation No.68 year 2013. Institute for Human and Machine Cognition (IHMC) has developed CmapTools, a client-server software for easily construct and visualize concept maps. This research aims to investigate secondary students' conceptual change after experiencing five-stage conceptual teaching model by utilizing CmapTools in learning Optics. Weak experimental method through one group pretest-posttest design is implemented in this study to collect preliminary and post concept map as qualitative data. Sample was taken purposively of 8th grade students (n= 22) at one of private schools Bandung, West Java. Conceptual change based on comparison of preliminary and post concept map construction is assessed based on rubric of concept map scoring and structure. Results shows significance conceptual change differences at 50.92 % that is elaborated into concept map element such as prepositions and hierarchical level in high category, cross links in medium category and specific examples in low category. All of the results are supported with the students' positive response towards CmapTools utilization that indicates improvement of motivation, interest, and behavior aspect towards Physics lesson.

Fish connectivity mapping intermediate data files and outputs

EPA Pesticide Factsheets

RLWrankedLists.tar.gz:These lists linked to various chemical treatment conditions serve as the target collection of Cmap. Probes of the entire microarray are sorted based on their log fold changes over control conditions. RLWsignatures2015.tar.gz: These signatures linked to various chemical treatment conditions serve as queries in Cmap.This dataset is associated with the following publication:Wang , R., A. Biales , N. Garcia-Reyero, E. Perkins, D. Villeneuve, G. Ankley, and D. Bencic. Fish Connectivity Mapping: Linking Chemical Stressors by Their MOA-Driven Transcriptomic Profiles. BMC Genomics. BioMed Central Ltd, London, UK, 17(84): 1-20, (2016).

Identification of alsterpaullone as a novel small molecule inhibitor to target group 3 medulloblastoma.

PubMed

Faria, Claudia C; Agnihotri, Sameer; Mack, Stephen C; Golbourn, Brian J; Diaz, Roberto J; Olsen, Samantha; Bryant, Melissa; Bebenek, Matthew; Wang, Xin; Bertrand, Kelsey C; Kushida, Michelle; Head, Renee; Clark, Ian; Dirks, Peter; Smith, Christian A; Taylor, Michael D; Rutka, James T

2015-08-28

Advances in the molecular biology of medulloblastoma revealed four genetically and clinically distinct subgroups. Group 3 medulloblastomas are characterized by frequent amplifications of the oncogene MYC, a high incidence of metastasis, and poor prognosis despite aggressive therapy. We investigated several potential small molecule inhibitors to target Group 3 medulloblastomas based on gene expression data using an in silico drug screen. The Connectivity Map (C-MAP) analysis identified piperlongumine as the top candidate drug for non-WNT medulloblastomas and the cyclin-dependent kinase (CDK) inhibitor alsterpaullone as the compound predicted to have specific antitumor activity against Group 3 medulloblastomas. To validate our findings we used these inhibitors against established Group 3 medulloblastoma cell lines. The C-MAP predicted drugs reduced cell proliferation in vitro and increased survival in Group 3 medulloblastoma xenografts. Alsterpaullone had the highest efficacy in Group 3 medulloblastoma cells. Genomic profiling of Group 3 medulloblastoma cells treated with alsterpaullone confirmed inhibition of cell cycle-related genes, and down-regulation of MYC. Our results demonstrate the preclinical efficacy of using a targeted therapy approach for Group 3 medulloblastomas. Specifically, we provide rationale for advancing alsterpaullone as a targeted therapy in Group 3 medulloblastoma.

[Study on effects of bioelectric parameters of rats in electromagnetic radiation of HV transmission line].

PubMed

Zhang, Anying; Pang, Xiaofeng; Yuan, Ping

2007-02-01

With the development of economy and coming of information era, the chance of exposure to electromagnetic fields with various frequencies has been increased for every human. The effects of electromagnetic radiattion on human being's health are versatile. To study the effects of bioelctronic parameters of rats in the electromagnetic radiations of HV transmission line, EEG, ECG and CMAP were measured in rats exposed to simulating high-voltage transmission line electromagnetic radiation for over one year. Brain tissues were studied by Fourier transform infrared spectroscopy. The results showed that no significant difference between exposed group and control group in EEG; however the FT-infrared spectra of brain tissues were different; the ECG of the exposed animals was considerably altered. Significant slowing of heart rate was observed in those rates exposed to EMFs; the latent period of CMAP in exposed group were not different compared with those of control group however there was a significant difference in wave amplitude of CMAP between the exposed group and control group. All results indicated that there must be some effects on bioelectric parameters of rats exposed to electromagnetic radiation of high-voltage transmission line for a long time.

The use of concept maps for knowledge management: from classrooms to research labs.

PubMed

Correia, Paulo Rogério Miranda

2012-02-01

Our contemporary society asks for new strategies to manage knowledge. The main activities developed by academics involve knowledge transmission (teaching) and production (research). Creativity and collaboration are valuable assets for establishing learning organizations in classrooms and research labs. Concept mapping is a useful graphical technique to foster some of the disciplines required to create and develop high-performance teams. The need for a linking phrase to clearly state conceptual relationships makes concept maps (Cmaps) very useful for organizing our own ideas (externalization), as well as, sharing them with other people (elicitation and consensus building). The collaborative knowledge construction (CKC) is supported by Cmaps because they improve the communication signal-to-noise ratio among participants with high information asymmetry. In other words, we can identify knowledge gaps and insightful ideas in our own Cmaps when discussing them with our counterparts. Collaboration involving low and high information asymmetry can also be explored through peer review and student-professor/advisor interactions, respectively. In conclusion, when it is used properly, concept mapping can provide a competitive advantage to produce and share knowledge in our contemporary society. To map is to know, as stated by Wandersee in 1990.

Sequestering CO2 in the Built Environment

NASA Astrophysics Data System (ADS)

Constantz, B. R.

2009-12-01

Calera’s Carbonate Mineralization by Aqueous Precipitation (CMAP) technology with beneficial reuse has been called, “game-changing” by Carl Pope, Director of the Sierra Club. Calera offers a solution to the scale of the carbon problem. By capturing carbon into the built environment through carbonate mineralization, Calera provides a sound and cost-effective alternative to Geologic Sequestration and Terrestrial Sequestration. The CMAP technology permanently converts carbon dioxide into a mineral form that can be stored above ground, or used as a building material. The process produces a suite of carbonate-containing minerals of various polymorphic forms. Calera product can be substituted into blends with ordinary Portland cements and used as aggregate to produce concrete with reduced carbon, carbon neutral, or carbon negative footprints. For each ton of product produced, approximately half a ton of carbon dioxide can be sequestered using the Calera process. Coal and natural gas are composed of predominately istopically light carbon, as the carbon in the fuel is plant-derived. Thus, power plant CO2 emissions have relatively low δ13C values.The carbon species throughout the CMAP process are identified through measuring the inorganic carbon content, δ13C values of the dissolved carbonate species, and the product carbonate minerals. Measuring δ13C allows for tracking the flue gas CO2 throughout the capture process. Initial analysis of the capture of propane flue gas (δ13C ˜ -25 ‰) with seawater (δ13C ˜ -10 ‰) and industrial brucite tailings from a retired magnesium oxide plant in Moss Landing, CA (δ13C ˜ -7 ‰ from residual calcite) produced carbonate mineral products with a δ13C value of ˜ -20 ‰. This isotopically light carbon, transformed from flue gas to stable carbonate minerals, can be transferred and tracked through the capture process, and finally to the built environment. CMAP provides an economical solution to global warming by producing a usable product. While the cost of this process may, in some cases, exceed the selling price of the resultant materials, the value produced combined with available carbon credits makes this CMAP technology economically and environmentally sustainable. Calera operates a pilot plant in Moss Landing, CA, which is within the Monterey Bay Marine Sanctuary. The pilot plant is complete with a coal-fired burner simulator (CFBS) and laboratory. During operation, seawater is drawn in and subsequently combined with a variety of natural and manufactured minerals. Propane or coal flue gas from the CFBS is then contacted with the slurry suspension. The precipitated minerals are separated from the seawater and are further processed to produce cement or other building materials. After the seawater flows through the Calera process, it is returned to the ocean largely unchanged, with the exception of being calcium and magnesium depleted. An overview of the process, reporting the δ13C values throughout the CMAP process, along with the risk involved in changing regulations will be presented.

Handling knowledge via Concept Maps: a space weather use case

NASA Astrophysics Data System (ADS)

Messerotti, Mauro; Fox, Peter

Concept Maps (Cmaps) are powerful means for knowledge coding in graphical form. As flexible software tools exist to manipulate the knowledge embedded in Cmaps in machine-readable form, such complex entities are suitable candidates not only for the representation of ontologies and semantics in Virtual Observatory (VO) architectures, but also for knowledge handling and knowledge discovery. In this work, we present a use case relevant to space weather applications and we elaborate on its possible implementation and adavanced use in Semantic Virtual Observatories dedicated to Sun-Earth Connections. This analysis was carried out in the framework of the Electronic Geophysical Year (eGY) and represents an achievement synergized by the eGY Virtual Observatories Working Group.

Connection Map for Compounds (CMC): A Server for Combinatorial Drug Toxicity and Efficacy Analysis.

PubMed

Liu, Lei; Tsompana, Maria; Wang, Yong; Wu, Dingfeng; Zhu, Lixin; Zhu, Ruixin

2016-09-26

Drug discovery and development is a costly and time-consuming process with a high risk for failure resulting primarily from a drug's associated clinical safety and efficacy potential. Identifying and eliminating inapt candidate drugs as early as possible is an effective way for reducing unnecessary costs, but limited analytical tools are currently available for this purpose. Recent growth in the area of toxicogenomics and pharmacogenomics has provided with a vast amount of drug expression microarray data. Web servers such as CMap and LTMap have used this information to evaluate drug toxicity and mechanisms of action independently; however, their wider applicability has been limited by the lack of a combinatorial drug-safety type of analysis. Using available genome-wide drug transcriptional expression profiles, we developed the first web server for combinatorial evaluation of toxicity and efficacy of candidate drugs named "Connection Map for Compounds" (CMC). Using CMC, researchers can initially compare their query drug gene signatures with prebuilt gene profiles generated from two large-scale toxicogenomics databases, and subsequently perform a drug efficacy analysis for identification of known mechanisms of drug action or generation of new predictions. CMC provides a novel approach for drug repositioning and early evaluation in drug discovery with its unique combination of toxicity and efficacy analyses, expansibility of data and algorithms, and customization of reference gene profiles. CMC can be freely accessed at http://cadd.tongji.edu.cn/webserver/CMCbp.jsp .

Neuromuscular Adaptations to Reduced Use

NASA Technical Reports Server (NTRS)

Ploutz-Snyder, Lori

2009-01-01

This viewgraph presentation reviews the studies done to reduce neuromuscular strength loss during unilateral lower limb suspension (ULLS). Since there are animals that undergo fairly long periods of muscular disuse without any or minimal muscular atrophy, there is an answer to that might be applicable to human in situations that require no muscular use to diminish the effects of muscular atrophy. Three sets of ULLS studies were reviewed indicated that muscle strength decreased more than the muscle mass. The study reviewed exercise countermeasures to combat the atrophy, including: ischemia maintained during Compound muscle action potential (CMAP), ischemia and low load exercise, Japanese kaatsu, and the potential for rehabilitation or situations where heavy loading is undesirable. Two forms of countermeasures to unloading have been successful, (1) high-load resistance training has maintained muscle mass and strength, and low load resistance training with blood flow restriction (LL(sub BFR)). The LL(sub BFR) has been shown to increase muscle mass and strength. There has been significant interest in Tourniquet training. An increase in Growth Hormone(GH) has been noted for LL(sub BFR) exercise. An experimental study with 16 subjects 8 of whom performed ULLS, and 8 of whom performed ULLS and LL(sub BFR) exercise three times per week during the ULLS. Charts show the results of the two groups, showing that performing LL(sub BFR) exercise during 30 days of ULLS can maintain muscle size and strength and even improve muscular endurance.

CMT2C with vocal cord paresis associated with short stature and mutations in the TRPV4 gene

PubMed Central

Chen, D.-H.; Sul, Y.; Weiss, M.; Hillel, A.; Lipe, H.; Wolff, J.; Matsushita, M.; Raskind, W.; Bird, T.

2010-01-01

Background: Recently, mutations in the transient receptor potential cation channel, subfamily V, member 4 gene (TRPV4) have been reported in Charcot-Marie-Tooth Type 2C (CMT2C) with vocal cord paresis. Other mutations in this same gene have been described in separate families with various skeletal dysplasias. Further clarification is needed of the different phenotypes associated with this gene. Methods: We performed clinical evaluation, electrophysiology, and genetic analysis of the TRPV4 gene in 2 families with CMT2C. Results: Two multigenerational families had a motor greater than sensory axonal neuropathy associated with variable vocal cord paresis. The vocal cord paresis varied from absent to severe, requiring permanent tracheotomy in 2 subjects. One family with mild neuropathy also manifested pronounced short stature, more than 2 SD below the average height for white Americans. There was one instance of dolichocephaly. A novel S542Y mutation in the TRPV4 gene was identified in this family. The other family had a more severe, progressive, motor neuropathy with sensory loss, but less remarkable short stature and an R315W mutation in TRPV4. Third cranial nerve involvement and sleep apnea occurred in one subject in each family. Conclusion: CMT2C with axonal neuropathy, vocal cord paresis, and short stature is a unique syndrome associated with mutations in the TRPV4 gene. Mutations in TRPV4 can cause abnormalities in bone, peripheral nerve, or both and may result in highly variable orthopedic and neurologic phenotypes. GLOSSARY CMAP = compound muscle action potential; CMT = Charcot-Marie-Tooth; CMT2C = Charcot-Marie-Tooth Type 2C; HMSN = hereditary motor and sensory neuropathy; NCV = nerve conduction velocity; RFLP = restriction fragment length polymorphism; SMA = spinal muscular atrophy; SNAP = sensory nerve action potential; SPSMA = scapuloperoneal spinal muscular atrophy. PMID:21115951

Radiation protective effects of baclofen predicted by a computational drug repurposing strategy.

PubMed

Ren, Lei; Xie, Dafei; Li, Peng; Qu, Xinyan; Zhang, Xiujuan; Xing, Yaling; Zhou, Pingkun; Bo, Xiaochen; Zhou, Zhe; Wang, Shengqi

2016-11-01

Exposure to ionizing radiation causes damage to living tissues; however, only a small number of agents have been approved for use in radiation injuries. Radioprotector is the primary countermeasure to radiation injury and none radioprotector has indeed reached the drug development stage. Repurposing the long list of approved, non-radioprotective drugs is an attractive strategy to find new radioprotective agents. Here, we applied a computational approach to discover new radioprotectors in silico by comparing publicly available gene expression data of ionizing radiation-treated samples from the Gene Expression Omnibus (GEO) database with gene expression signatures of more than 1309 small-molecule compounds from the Connectivity Map (cmap) dataset. Among the best compounds predicted to be therapeutic for ionizing radiation damage by this approach were some previously reported radioprotectors and baclofen (P<0.01), a chemical that was not previously used as radioprotector. Validation using a cell-based model and a rodent in vivo model demonstrated that treatment with baclofen reduced radiation-induced cytotoxicity in vitro (P<0.01), attenuated bone marrow damage and increased survival in vivo (P<0.05). These findings suggest that baclofen might serve as a radioprotector. The drug repurposing strategy by connecting the GEO data and cmap can be used to identify known drugs as potential radioprotective agents. Copyright © 2016 Elsevier Ltd. All rights reserved.

Evaluation of high-density, multi-contact nerve cuffs for activation of grasp muscles in monkeys

NASA Astrophysics Data System (ADS)

Brill, N. A.; Naufel, S. N.; Polasek, K.; Ethier, C.; Cheesborough, J.; Agnew, S.; Miller, L. E.; Tyler, D. J.

2018-06-01

Objective. The objective of this work was to evaluate whether nerve cuffs can selectively activate hand muscles for functional electrical stimulation (FES). FES typically involves identifying and implanting electrodes in many individual muscles, but nerve cuffs only require implantation at a single site around the nerve. This method is surgically more attractive. Nerve cuffs may also more effectively stimulate intrinsic hand muscles, which are difficult to implant and stimulate without spillover to adjacent muscles. Approach. To evaluate its ability to selectively activate muscles, we implanted and tested the flat interface nerve electrode (FINE), which is designed to selectively stimulate peripheral nerves that innervate multiple muscles (Tyler and Durand 2002 IEEE Trans. Neural Syst. Rehabil. Eng. 10 294-303). We implanted FINEs on the nerves and bipolar intramuscular wires for recording compound muscle action potentials (CMAPs) from up to 20 muscles in each arm of six monkeys. We then collected recruitment curves while the animals were anesthetized. Main result. A single FINE implanted on an upper extremity nerve in the monkey can selectively activate muscles or small groups of muscles to produce multiple, independent hand functions. Significance. FINE cuffs can serve as a viable supplement to intramuscular electrodes in FES systems, where they can better activate intrinsic and extrinsic muscles with lower currents and less extensive surgery.

Molecular Mechanisms of Treadmill Therapy on Neuromuscular Atrophy Induced via Botulinum Toxin A

PubMed Central

Tsai, Sen-Wei; Chen, Hsiao-Ling

2013-01-01

Botulinum toxin A (BoNT-A) is a bacterial zinc-dependent endopeptidase that acts specifically on neuromuscular junctions. BoNT-A blocks the release of acetylcholine, thereby decreasing the ability of a spastic muscle to generate forceful contraction, which results in a temporal local weakness and the atrophy of targeted muscles. BoNT-A-induced temporal muscle weakness has been used to manage skeletal muscle spasticity, such as poststroke spasticity, cerebral palsy, and cervical dystonia. However, the combined effect of treadmill exercise and BoNT-A treatment is not well understood. We previously demonstrated that for rats, following BoNT-A injection in the gastrocnemius muscle, treadmill running improved the recovery of the sciatic functional index (SFI), muscle contraction strength, and compound muscle action potential (CMAP) amplitude and area. Treadmill training had no influence on gastrocnemius mass that received BoNT-A injection, but it improved the maximal contraction force of the gastrocnemius, and upregulation of GAP-43, IGF-1, Myo-D, Myf-5, myogenin, and acetylcholine receptor (AChR) subunits α and β was found following treadmill training. Taken together, these results suggest that the upregulation of genes associated with neurite and AChR regeneration following treadmill training may contribute to enhanced gastrocnemius strength recovery following BoNT-A injection. PMID:24327926

Comparative study of peripheral neuropathy and nerve regeneration in NOD and ICR diabetic mice.

PubMed

Homs, Judit; Ariza, Lorena; Pagès, Gemma; Verdú, Enrique; Casals, Laura; Udina, Esther; Chillón, Miguel; Bosch, Assumpció; Navarro, Xavier

2011-09-01

The non-obese diabetic (NOD) mouse was suggested as an adequate model for diabetic autonomic neuropathy. We evaluated sensory-motor neuropathy and nerve regeneration following sciatic nerve crush in NOD males rendered diabetic by multiple low doses of streptozotocin, in comparison with similarly treated Institute for Cancer Research (ICR) mice, a widely used model for type I diabetes. Neurophysiological values for both strains showed a decline in motor and sensory nerve conduction velocity at 7 and 8 weeks after induction of diabetes in the intact hindlimb. However, amplitudes of compound muscle and sensory action potentials (CMAPs and CNAPs) were significantly reduced in NOD but not in ICR diabetic mice. Morphometrical analysis showed myelinated fiber loss in highly hyperglycemic NOD mice, but no significant changes in fiber size. There was a reduction of intraepidermal nerve fibers, more pronounced in NOD than in ICR diabetic mice. Interestingly, aldose reductase and poly(ADP-ribose) polymerase (PARP) activities were increased already at 1 week of hyperglycemia, persisting until the end of the experiment in both strains. Muscle and nerve reinnervation was delayed in diabetic mice following sciatic nerve crush, being more marked in NOD mice. Thus, diabetes of mid-duration induces more severe peripheral neuropathy and slower nerve regeneration in NOD than in ICR mice. © 2011 Peripheral Nerve Society.

WheatGenome.info: A Resource for Wheat Genomics Resource.

PubMed

Lai, Kaitao

2016-01-01

An integrated database with a variety of Web-based systems named WheatGenome.info hosting wheat genome and genomic data has been developed to support wheat research and crop improvement. The resource includes multiple Web-based applications, which are implemented as a variety of Web-based systems. These include a GBrowse2-based wheat genome viewer with BLAST search portal, TAGdb for searching wheat second generation genome sequence data, wheat autoSNPdb, links to wheat genetic maps using CMap and CMap3D, and a wheat genome Wiki to allow interaction between diverse wheat genome sequencing activities. This portal provides links to a variety of wheat genome resources hosted at other research organizations. This integrated database aims to accelerate wheat genome research and is freely accessible via the web interface at http://www.wheatgenome.info/ .

Exploring physics concepts among novice teachers through CMAP tools

NASA Astrophysics Data System (ADS)

Suprapto, N.; Suliyanah; Prahani, B. K.; Jauhariyah, M. N. R.; Admoko, S.

2018-03-01

Concept maps are graphical tools for organising, elaborating and representing knowledge. Through Cmap tools software, it can be explored the understanding and the hierarchical structuring of physics concepts among novice teachers. The software helps physics teachers indicated a physics context, focus questions, parking lots, cross-links, branching, hierarchy, and propositions. By using an exploratory quantitative study, a total 13-concept maps with different physics topics created by novice physics teachers were analysed. The main differences of scoring between lecturer and peer-teachers’ scoring were also illustrated. The study offered some implications, especially for physics educators to determine the hierarchical structure of the physics concepts, to construct a physics focus question, and to see how a concept in one domain of knowledge represented on the map is related to a concept in another domain shown on the map.

Notification: Review of the Contract Management Assessment Program

EPA Pesticide Factsheets

Project #OA-FY14-0034, October 30, 2013. The Office of Inspector General plans to begin the preliminary research phase of an audit evaluating the Office of Acquisition Management’s Contract Management Assessment Program (CMAP).

Vibration upshot of operating mechanical sewing machine: an insight into common peroneal nerve conduction study.

PubMed

Yadav, Prakash Kumar; Yadav, Ram Lochan; Sharma, Deepak; Shah, Dev Kumar; Sapkota, Niraj Khatri; Thakur, Dilip; Limbu, Nirmala; Islam, Md Nazrul

2017-01-01

Most of the people associated with tailoring occupation in Nepal are still using mechanical sewing machine as an alternative of new technology for tailoring. Common peroneal nerves of both right and left legs are exposed to strenuous and chronic stress exerted by vibration and paddling of mechanical sewing machine. The study included 30 healthy male tailors and 30 healthy male individuals. Anthropometric variables as well as cardio respiratory variables were determined for each subject. Standard Nerve Conduction Techniques using constant measured distances were applied to evaluate common peroneal nerve (motor) in both legs of each individual. Data were analyzed and compared between study and control groups using Man Whitney U test setting the significance level p  ≤ 0.05. Anthropometric and cardio respiratory variables were not significantly altered between the study and control groups. The Compound muscle action potential (CMAP) latency of common peroneal nerves of both right [(11.29 ± 1.25 vs. 10.03 ± 1.37), P  < 0.001] and left [(11.28 ± 1.38 vs. 10.05 ± 1.37), P  < 0.01] legs was found to be significantly prolonged in study group as compared to control group. The Amp-CMAP of common peroneal nerves of both right [(4.57 ± 1.21 vs. 6.22 ± 1.72), P  < 0.001] and left [(4.31 ± 1.55 vs. 6.25 ± 1.70), P  < 0.001] legs was found significantly reduced in study group as compared to control group. Similarly, the motor nerve conduction velocity (MNCV) of common peroneal nerves of both right [(43.72 ± 3.25 vs. 47.49 ± 4.17), P  < 0.001] and left [(42.51 ± 3.82 vs. 46.76 ± 4.51), P  < 0.001] legs was also found to be significantly reduced in study group in comparison to control group. Operating mechanical sewing machine by paddling chronically and arduously could have attributed to abnormal nerve conduction study parameters due to vibration effect of the machine on right and left common peroneal nerves. The results of present study follow the trend towards presymptomatic or asymptomatic neuropathy similar to subclinical neuropathy.

Cancer in silico drug discovery: a systems biology tool for identifying candidate drugs to target specific molecular tumor subtypes.

PubMed

San Lucas, F Anthony; Fowler, Jerry; Chang, Kyle; Kopetz, Scott; Vilar, Eduardo; Scheet, Paul

2014-12-01

Large-scale cancer datasets such as The Cancer Genome Atlas (TCGA) allow researchers to profile tumors based on a wide range of clinical and molecular characteristics. Subsequently, TCGA-derived gene expression profiles can be analyzed with the Connectivity Map (CMap) to find candidate drugs to target tumors with specific clinical phenotypes or molecular characteristics. This represents a powerful computational approach for candidate drug identification, but due to the complexity of TCGA and technology differences between CMap and TCGA experiments, such analyses are challenging to conduct and reproduce. We present Cancer in silico Drug Discovery (CiDD; scheet.org/software), a computational drug discovery platform that addresses these challenges. CiDD integrates data from TCGA, CMap, and Cancer Cell Line Encyclopedia (CCLE) to perform computational drug discovery experiments, generating hypotheses for the following three general problems: (i) determining whether specific clinical phenotypes or molecular characteristics are associated with unique gene expression signatures; (ii) finding candidate drugs to repress these expression signatures; and (iii) identifying cell lines that resemble the tumors being studied for subsequent in vitro experiments. The primary input to CiDD is a clinical or molecular characteristic. The output is a biologically annotated list of candidate drugs and a list of cell lines for in vitro experimentation. We applied CiDD to identify candidate drugs to treat colorectal cancers harboring mutations in BRAF. CiDD identified EGFR and proteasome inhibitors, while proposing five cell lines for in vitro testing. CiDD facilitates phenotype-driven, systematic drug discovery based on clinical and molecular data from TCGA. ©2014 American Association for Cancer Research.

WheatGenome.info: an integrated database and portal for wheat genome information.

PubMed

Lai, Kaitao; Berkman, Paul J; Lorenc, Michal Tadeusz; Duran, Chris; Smits, Lars; Manoli, Sahana; Stiller, Jiri; Edwards, David

2012-02-01

Bread wheat (Triticum aestivum) is one of the most important crop plants, globally providing staple food for a large proportion of the human population. However, improvement of this crop has been limited due to its large and complex genome. Advances in genomics are supporting wheat crop improvement. We provide a variety of web-based systems hosting wheat genome and genomic data to support wheat research and crop improvement. WheatGenome.info is an integrated database resource which includes multiple web-based applications. These include a GBrowse2-based wheat genome viewer with BLAST search portal, TAGdb for searching wheat second-generation genome sequence data, wheat autoSNPdb, links to wheat genetic maps using CMap and CMap3D, and a wheat genome Wiki to allow interaction between diverse wheat genome sequencing activities. This system includes links to a variety of wheat genome resources hosted at other research organizations. This integrated database aims to accelerate wheat genome research and is freely accessible via the web interface at http://www.wheatgenome.info/.

Effects of Source-Apportioned Coarse Particulate Matter (PM) on Allergic Responses in Mice

EPA Science Inventory

The Cleveland Multiple Air Pollutant Study (CMAPS) is one of the first comprehensive studies conducted to evaluate particulate matter (PM) over local and regional scales. Cleveland and the nearby Ohio River Valley impart significant regional sources of air pollution including coa...

Quantifying Qualitative Data Using Cognitive Maps

ERIC Educational Resources Information Center

Scherp, Hans-Ake

2013-01-01

The aim of the article is to show how substantial qualitative material consisting of graphic cognitive maps can be analysed by using digital CmapTools, Excel and SPSS. Evidence is provided of how qualitative and quantitative methods can be combined in educational research by transforming qualitative data into quantitative data to facilitate…

The relationship between preoperative needle electromyography findings and muscle power restoration after surgery in severe carpal tunnel syndrome patients.

PubMed

Hara, Yuki; Nishiura, Yasumasa; Ochiai, Naoyuki; Murai, Shinji; Yamazaki, Masashi

2017-05-01

Needle electromyography provides essential information about the functional aspects of the muscle. But little attention has been given in the literature to needle electromyography examinations in carpal tunnel syndrome. We examined the relationship between preoperative needle electromyography findings and functional recovery of the abductor pollicis brevis (APB) muscle in severe carpal tunnel syndrome patients. The subjects of this study were 49 patients, 58 hands, who fit the following 5 criteria: (1) idiopathic carpal tunnel syndrome; (2) pre-op MMT grade of the APB muscle was M0 or M1; (3) APB-CMAP (compound muscle action potential) was not evoked in a median nerve conduction study; (4) needle electromyography of the APB muscle had been done; (5) underwent carpal tunnel release only. The patients were divided into two groups according to the results of pre-op needle electromyography: voluntary motor unit potential of the APB muscle was evoked [MUP(+) group]or not [MUP(-) group]. We evaluated APB muscle strength at one year after surgery, and patient satisfaction and functional evaluations (CTSI-FS) at more than one year after. The APB muscle recovery rate to M3 or higher was 100% in the MUP(+) group, and 57% in the MUP(-) group. Patient satisfaction was also high and functional recovery was sufficient in the MUP(+) group. No patients requested a second opponensplasty. Our findings suggest that post-op restoration of thumb function relates to whether or not the MUP ofthe APB muscle is evoked. Single-stage opponensplasty may be unnecessary if the MUP of the APB muscle is; evoked. Needle electromyography is therefore useful in consideration for opponensplasty. Level Ⅲ, case-control study. Copyright © 2017. Published by Elsevier B.V.

[Food-borne botulism].

PubMed

Nakamura, Yuko; Sawada, Mikio; Ikeguchi, Kunihiko; Nakano, Imaharu

2011-09-01

Botulism is a neuroparalytic disease caused by neurotoxins produced by Clostridium botulinum. Food-borne botulism is a kind of exotoxin-caused food intoxication. Although this disease is rarely reported in Japan now, it is a cause of great concern because of its high mortality rate, and botulism cases should be treated as a public health emergency. Botulism classically presents as acute symmetrical descending flaccid paralysis. Its diagnosis is based on the detection of botulinum toxins in the patient's serum or stool specimens. Electrophysiologic tests of such patients show reduced compound muscle action potentials (CMAPs), low amplitudes and short durations of motor unit potentials (MUPs), and mild waning in repetitive low-frequency stimulations. Single fiber electromyography (EMG) is particularly useful for the diagnosis of botulism. We report a case of food-borne botulism that we had encountered. An 83-year-old man with rapidly progressive diplopia, dysphagia, and tetraplegia was hospitalized; he required intensive care, including artificial ventilatory support. Electrophysiologic tests yielded findings compatible with botulism. We made a clinical diagnosis of food-borne botulism and administered antitoxin on the seventh disease day. The patient's motor symptoms started ameliorating several days after the antitoxin injection. Subsequently, botulinum toxin type A was detected in the patient's serum specimen by using a bioassay, and the type A gene and silent B gene were detected in his serum specimen by using polymerase chain reaction (PCR). C. botulinum was also obtained from stool culture on the 17th and 50th disease days. Botulism is a curable disease if treated early. Although it is a rare condition, it should always be considered in the differential diagnosis of patients with rapid onset of cranial nerve and limb muscle palsies.

Transposition of branches of radial nerve innervating supinator to posterior interosseous nerve for functional reconstruction of finger and thumb extension in 4 patients with middle and lower trunk root avulsion injuries of brachial plexus.

PubMed

Wu, Xia; Cong, Xiao-Bing; Huang, Qi-Shun; Ai, Fang-Xin; Liu, Yu-Tian; Lu, Xiao-Cheng; Li, Jin; Weng, Yu-Xiong; Chen, Zhen-Bing

2017-12-01

This study aimed to investigate the reconstruction of the thumb and finger extension function in patients with middle and lower trunk root avulsion injuries of the brachial plexus. From April 2010 to January 2015, we enrolled in this study 4 patients diagnosed with middle and lower trunk root avulsion injuries of the brachial plexus via imaging tests, electrophysiological examinations, and clinical confirmation. Muscular branches of the radial nerve, which innervate the supinator in the forearm, were transposed to the posterior interosseous nerve to reconstruct the thumb and finger extension function. Electrophysiological findings and muscle strength of the extensor pollicis longus and extensor digitorum communis, as well as the distance between the thumb tip and index finger tip, were monitored. All patients were followed up for 24 to 30 months, with an average of 27.5 months. Motor unit potentials (MUP) of the extensor digitorum communis appeared at an average of 3.8 months, while MUP of the extensor pollicis longus appeared at an average of 7 months. Compound muscle action potential (CMAP) appeared at an average of 9 months in the extensor digitorum communis, and 12 months in the extensor pollicis longus. Furthermore, the muscle strength of the extensor pollicis longus and extensor digitorum communis both reached grade III at 21 months. Lastly, the average distance between the thumb tip and index finger tip was 8.8 cm at 21 months. In conclusion, for patients with middle and lower trunk injuries of the brachial plexus, transposition of the muscular branches of the radial nerve innervating the supinator to the posterior interosseous nerve for the reconstruction of thumb and finger extension function is practicable and feasible.

Overexpression of mutant HSP27 causes axonal neuropathy in mice.

PubMed

Lee, Jinho; Jung, Sung-Chul; Joo, Jaesoon; Choi, Yu-Ri; Moon, Hyo Won; Kwak, Geon; Yeo, Ha Kyung; Lee, Ji-Su; Ahn, Hye-Jee; Jung, Namhee; Hwang, Sunhee; Rheey, Jingeun; Woo, So-Youn; Kim, Ji Yon; Hong, Young Bin; Choi, Byung-Ok

2015-06-19

Mutations in heat shock 27 kDa protein 1 (HSP27 or HSPB1) cause distal hereditary motor neuropathy (dHMN) or Charcot-Marie-Tooth disease type 2 F (CMT2F) according to unknown factors. Mutant HSP27 proteins affect axonal transport by reducing acetylated tubulin. We generated a transgenic mouse model overexpressing HSP27-S135F mutant protein driven by Cytomegalovirus (CMV) immediate early promoter. The mouse phenotype was similar to dHMN patients in that they exhibit motor neuropathy. To determine the phenotypic aberration of transgenic mice, behavior test, magnetic resonance imaging (MRI), electrophysiological study, and pathology were performed. Rotarod test showed that founder mice exhibited lowered motor performance. MRI also revealed marked fatty infiltration in the anterior and posterior compartments at calf level. Electrophysiologically, compound muscle action potential (CMAP) but not motor nerve conduction velocity (MNCV) was reduced in the transgenic mice. Toluidine staining with semi-thin section of sciatic nerve showed the ratio of large myelinated axon fiber was reduced, which might cause reduced locomotion in the transgenic mice. Electron microscopy also revealed abundant aberrant myelination. Immunohistochemically, neuronal dysfunctions included elevated level of phosphorylated neurofilament and reduced level of acetylated tubulin in the sural nerve of transgenic mice. There was no additional phenotype besides motor neuronal defects. Overexpression of HSP27-S135F protein causes peripheral neuropathy. The mouse model can be applied to future development of therapeutic strategies for dHMN or CMT2F.

Laser-activated protein bands for peripheral nerve repair

NASA Astrophysics Data System (ADS)

Lauto, Antonio; Trickett, Rodney I.; Malik, Richard; Dawes, Judith M.; Owen, Earl R.

1996-01-01

A 100 micrometer core optical fiber-coupled 75 mW diode laser operating at a wavelength of 800 nm has been used in conjunction with a protein solder to stripe weld severed rat tibial nerves, reducing the long operating time required for microsurgical nerve repair. Welding is produced by selective laser denaturation of the protein based solder which contains the dye indocyanine green. Operating time for laser soldering was 10 plus or minus 5 min. (n equals 24) compared to 23 plus or minus 9 min (n equals 13) for microsuturing. The laser solder technique resulted in patent welds with a tensile strength of 15 plus or minus 5 g, while microsutured nerves had a tensile strength of 40 plus or minus 10 g. Histopathology of the laser soldered nerves, conducted immediately after surgery, displayed solder adhesion to the outer membrane with minimal damage to the inner axons of the nerves. An in vivo study, with a total of fifty-seven adult male wistar rats, compared laser solder repaired tibial nerves to conventional microsuture repair. Twenty-four laser soldered nerves and thirteen sutured nerves were characterized at three months and showed successful regeneration with average compound muscle action potentials (CMAP) of 2.4 plus or minus 0.7 mV and 2.7 plus or minus 0.8 mV respectively. Histopathology of the in vivo study, confirmed the comparable regeneration of axons in laser and suture operated nerves. A faster, less damaging and long lasting laser based anastomotic technique is presented.

2007 Chicago Regional Household Travel Inventory | Transportation Secure

Science.gov Websites

period. In addition to traditional survey-based data collection, this study featured a sub-sample of processing and filtering routines. Survey Records Survey records include 460 households. More Information For more information about the survey, see the CMAP Regional Travel Survey Final Report. Transportation

A Presumption of Competence: Elementary Pre-Service Teacher Knowledge about Dissolving

ERIC Educational Resources Information Center

Harrell, Pamela; Subramaniam, Karthigeyan

2014-01-01

This study explored elementary pre-service teachers' content knowledge for dissolving before and after an instructional intervention over a 15-week science methods course. Pre-service teacher knowledge was examined using pre/post concept maps (Cmaps) and drawings with narrative descriptions. A mixed methods approach was used for both data…

Perspectives of Mobile Versus Fixed Mammography in Santa Clara County, California: A Focus Group Study.

PubMed

Chen, Yi-Ren; Chang-Halpenny, Christine; Kumarasamy, Narmadan A; Venegas, Angela; Braddock Iii, Clarence H

2016-02-12

Our aim was to examine underserved women's perceptions on mobile versus fixed mammography in Santa Clara, California through a focus group study.  Research has shown that medically underserved women have higher breast cancer mortality rates correlated with under-screening and a disproportional rate of late-stage diagnosis. The Community Health Partnership in Santa Clara County, California runs the Community Mammography Access Project (CMAP) that targets nearly 20,000 medically underserved women over the age of 40 in the county through the collaborative effort of an existing safety net of healthcare providers. However, little data exists on the advantages or disadvantages of mobile mammography units from the patient perspective.   We assessed underserved women's perspectives on mammography services in Santa Clara County through two focus groups from women screened at mobile or fixed site programs. Patients were recruited from both CMAP clinics and a county hospital, and focus group data were analyzed using content analysis.  We found that women from both the mobile and fixed sites shared similar motivating factors for getting a mammogram. Both groups recognized that screening was uncomfortable but necessary for good health and had positive feedback about their personal physicians. However, mobile participants, in particular, appreciated the atmosphere of mobile screening, reported shorter wait times, and remarked on the good communication from the clinic staff and empathetic treatment they received. However, mobile participants also expressed concern about the quality of films at mobile sites due to delayed initial reading of the films.   Mobile mammography offers a unique opportunity for women of underserved populations to access high satisfaction screenings, and it encourages a model similar to CMAP in other underserved areas. However, emphasis should be placed on providing a warm and welcoming environment for patients and ensuring the quality of mammography images.

The para-HK/QK correspondence

NASA Astrophysics Data System (ADS)

Dyckmanns, Malte; Vaughan, Owen

2017-06-01

We generalise the hyper-Kähler/quaternionic Kähler (HK/QK) correspondence to include para-geometries, and present a new concise proof that the target manifold of the HK/QK correspondence is quaternionic Kähler. As an application, we construct one-parameter deformations of the temporal and Euclidean supergravity c-map metrics and show that they are para-quaternionic Kähler.

Teaching Science with Technology: Case Studies of Science Teachers' Development of Technology, Pedagogy, and Content Knowledge

ERIC Educational Resources Information Center

Guzey, S. Selcen; Roehrig, Gillian H.

2009-01-01

This study examines the development of technology, pedagogy, and content knowledge (TPACK) in four in-service secondary science teachers as they participated in a professional development program focusing on technology integration into K-12 classrooms to support science as inquiry teaching. In the program, probeware, mind-mapping tools (CMaps),…

Constraining Carbonaceous Aerosol Sources in a Receptor Model Using Combined 14C, Redox Species, Organic Tracers, and Elementary/Organic Carbon Measurements

EPA Science Inventory

Sources of carbonaceous PM_2.5 were quantified in downtown Cleveland, OH and Chippewa Lake, OH located ~40 miles southwest of Cleveland during the Cleveland Multiple Air Pollutant Study (CMAPS). PM_2.5 filter samples were collected daily during July-August 200...

A Critical Review of Concept Mapping Research Literature: Informing Teaching and Learning Practices in GED Preparation Programs

ERIC Educational Resources Information Center

Martin, Larry G.; Martin, Fatima A.; Southworth, Erica

2015-01-01

Concept maps (Cmaps) are still underutilized in adult literacy programs and classes. The teaching and learning approaches that have been used historically in adult literacy programs to address the learning needs of these students have not kept pace with the literacy skill demands that have sprung from the increased pace of technological…

What Do EESD "Experts" Think Sustainability Is? Which Pedagogy Is Suitable to Learn It?: Results from Interviews and Cmaps Analysis Gathered at EESD 2008

ERIC Educational Resources Information Center

Segalas, Jordi; Mulder, Karel F.; Ferrer-Balas, Didac

2012-01-01

Purpose: The purpose of this paper is to study how experts on teaching sustainability in engineering education contextualize sustainability; also to evaluate the understanding of sustainability by engineering students. The final aim is to evaluate what pedagogy experts believe provides better opportunities for learning about sustainability in…

CmapTools: A Software Environment for Knowledge Modeling and Sharing

NASA Technical Reports Server (NTRS)

Canas, Alberto J.

2004-01-01

In an ongoing collaborative effort between a group of NASA Ames scientists and researchers at the Institute for Human and Machine Cognition (IHMC) of the University of West Florida, a new version of CmapTools has been developed that enable scientists to construct knowledge models of their domain of expertise, share them with other scientists, make them available to anybody on the Internet with access to a Web browser, and peer-review other scientists models. These software tools have been successfully used at NASA to build a large-scale multimedia on Mars and in knowledge model on Habitability Assessment. The new version of the software places emphasis on greater usability for experts constructing their own knowledge models, and support for the creation of large knowledge models with large number of supporting resources in the forms of images, videos, web pages, and other media. Additionally, the software currently allows scientists to cooperate with each other in the construction, sharing and criticizing of knowledge models. Scientists collaborating from remote distances, for example researchers at the Astrobiology Institute, can concurrently manipulate the knowledge models they are viewing without having to do this at a special videoconferencing facility.

Five years experience on 3,4-diaminopyridine phosphate in Lambert–Eaton syndrome

PubMed Central

Portaro, Simona; Brizzi, Teresa; Sinicropi, Stefano; Cacciola, Alberto; De Cola, Maria Cristina; Bramanti, Alessia; Milardi, Demetrio; Lupica, Antonino; Bramanti, Placido; Toscano, Antonio; Rodolico, Carmelo

2017-01-01

Abstract Rationale: To report our experience on 7 patients (4 males and 3 females), affected by nonparaneoplastic Lambert–Eaton myasthenic syndrome, treated with 3,4-diaminopyridine phosphate (3,4-DAPP) either alone or in combination with other immunosuppressants or steroids. Patient concerns: Patients have been evaluated at specific timepoints (ie, baseline and last 5 year follow-up), with neurological examination, autoantibodies against presynaptic voltage-gated Cav2.1 (P/Q type) calcium ion channel (VGCC) dosage, neurophysiological evaluation focusing on the increased amplitude of the compound muscle action potential (cMAP) after maximum voluntary effort, quantitative myasthenia gravis (QMG) and activities of daily living scales, and autonomic nervous system involvement evaluation. Outcomes: Five out of 7 patients presented a clinical improvement persisting at last 5-year follow-up; 2 out of them improved taking only 3,4-DAPP at the maximal dosage, whereas the remaining received concomitant medications, such as prednisone and azathioprine. However, the clinical amelioration was not statistically significant. No one of the patients reported severe adverse events, except one, complaining of transient chin and perioral paresthesias. A significant association between QMG and the type of pharmacological drugs therapy (P = .028) emerged. Indeed, we observed an improvement of the clinical condition in all 3 subjects treated with 3,4-DAPP and prednisone. Conclusions: In this study, we confirm 3,4-DAPP treatment efficacy on muscle strength, but minor evidence of drug effectiveness have been demonstrated on the autonomic nervous system involvement and on the deep tendon reflexes reappearance, a part from patients who received 3,4-DAPP associated to prednisone. PMID:28930822

Long-term outcomes in patients with ulnar neuropathy at the elbow treated according to the presumed aetiology.

PubMed

Omejec, Gregor; Podnar, Simon

2018-06-01

Ulnar neuropathy at the elbow (UNE) consists mainly of two conditions: entrapment under the humeroulnar aponeurosis (HUA) and extrinsic compression in the retrocondylar (RTC) groove. These in our opinion need different treatment: surgical HUA release and avoidance of inappropriate arm positioning, respectively. We treated our UNE patients accordingly, and studied their long-term outcomes. We invited our cohort of UNE patients to a follow-up examination consisting of history, neurological, electrodiagnostic (EDx) and ultrasonographic (US) examinations performed by four blinded investigators. At a mean follow-up time of 881 days, we performed a complete evaluation in 117 of 165 (65%) patients, with 96 (90%; 35 HUA and 61 RTC) treated according to our recommendations. An improvement was reported by 83% of HUA and 84% of RTC patients. In both groups the ulnar nerve mean compound muscle action potential (CMAP) amplitude, and the minimal motor nerve conduction velocity increased, while the maximal ulnar nerve cross-sectional area (CSA) decreased. After 2.5 years similar proportions of HUA and RTC patients reported clinical improvement that was supported by improvement in EDx and US findings. These results suggest that patients with UNE improve following both surgical decompression and non-operative treatment. A clinical trial comparing treatment approaches in neuropathy localised to the HUA and RTC will be needed to possibly confirm our opinion that the therapeutic approach should be tailored according to the presumed aetiology of UNE. Copyright © 2018 International Federation of Clinical Neurophysiology. Published by Elsevier B.V. All rights reserved.

CMAPS_ASPS_DATA-LCM_GTC

EPA Pesticide Factsheets

Total mercury in precipitation collected using ASPS automated wet-only instrument and analyzed by cold vapor atomic fluorescence spectroscopy.This dataset is associated with the following publication:Lynam, M., J.T. Dvonch, J. Barres, M. Landis , and A. Kamal. Investigating the impact of local urban sources on total atmospheric mercury wet deposition in Cleveland, Ohio, USA. ATMOSPHERIC ENVIRONMENT. Elsevier Science Ltd, New York, NY, USA, 127: 262-271, (2016).

Analyzing gene expression profiles in dilated cardiomyopathy via bioinformatics methods.

PubMed

Wang, Liming; Zhu, L; Luan, R; Wang, L; Fu, J; Wang, X; Sui, L

2016-10-10

Dilated cardiomyopathy (DCM) is characterized by ventricular dilatation, and it is a common cause of heart failure and cardiac transplantation. This study aimed to explore potential DCM-related genes and their underlying regulatory mechanism using methods of bioinformatics. The gene expression profiles of GSE3586 were downloaded from Gene Expression Omnibus database, including 15 normal samples and 13 DCM samples. The differentially expressed genes (DEGs) were identified between normal and DCM samples using Limma package in R language. Pathway enrichment analysis of DEGs was then performed. Meanwhile, the potential transcription factors (TFs) and microRNAs (miRNAs) of these DEGs were predicted based on their binding sequences. In addition, DEGs were mapped to the cMap database to find the potential small molecule drugs. A total of 4777 genes were identified as DEGs by comparing gene expression profiles between DCM and control samples. DEGs were significantly enriched in 26 pathways, such as lymphocyte TarBase pathway and androgen receptor signaling pathway. Furthermore, potential TFs (SP1, LEF1, and NFAT) were identified, as well as potential miRNAs (miR-9, miR-200 family, and miR-30 family). Additionally, small molecules like isoflupredone and trihexyphenidyl were found to be potential therapeutic drugs for DCM. The identified DEGs (PRSS12 and FOXG1), potential TFs, as well as potential miRNAs, might be involved in DCM.

Analyzing gene expression profiles in dilated cardiomyopathy via bioinformatics methods

PubMed Central

Wang, Liming; Zhu, L.; Luan, R.; Wang, L.; Fu, J.; Wang, X.; Sui, L.

2016-01-01

Dilated cardiomyopathy (DCM) is characterized by ventricular dilatation, and it is a common cause of heart failure and cardiac transplantation. This study aimed to explore potential DCM-related genes and their underlying regulatory mechanism using methods of bioinformatics. The gene expression profiles of GSE3586 were downloaded from Gene Expression Omnibus database, including 15 normal samples and 13 DCM samples. The differentially expressed genes (DEGs) were identified between normal and DCM samples using Limma package in R language. Pathway enrichment analysis of DEGs was then performed. Meanwhile, the potential transcription factors (TFs) and microRNAs (miRNAs) of these DEGs were predicted based on their binding sequences. In addition, DEGs were mapped to the cMap database to find the potential small molecule drugs. A total of 4777 genes were identified as DEGs by comparing gene expression profiles between DCM and control samples. DEGs were significantly enriched in 26 pathways, such as lymphocyte TarBase pathway and androgen receptor signaling pathway. Furthermore, potential TFs (SP1, LEF1, and NFAT) were identified, as well as potential miRNAs (miR-9, miR-200 family, and miR-30 family). Additionally, small molecules like isoflupredone and trihexyphenidyl were found to be potential therapeutic drugs for DCM. The identified DEGs (PRSS12 and FOXG1), potential TFs, as well as potential miRNAs, might be involved in DCM. PMID:27737314

Concept Mapping as a Support for Mars Landing-Site Selection

NASA Technical Reports Server (NTRS)

Cabrol, Nathalie A.; Briggs, Geoffrey A.

1999-01-01

The NASA Ames' Center for Mars Exploration (CMEX) serves to coordinate Mars programmatic research at ARC in the sciences, in information technology and in aero-assist and other technologies. Most recently, CMEX has been working with the Institute for Human and Machine Cognition at the University of West Florida to develop a new kind of web browser based on the application of concept maps. These Cmaps, which are demonstrably effective in science teaching, can be used to provide a new kind of information navigation tool that can make web or CD based information more meaningful and more easily navigable. CMEX expects that its 1999 CD-ROM will have this new user interface. CMEX is also engaged with the Mars Surveyor Project Office at JPL in developing an Internet-based source of materials to support the process of selecting landing sites for the next series of Mars landers. This activity -- identifying the most promising sites from which to return samples relevant to the search for evidence of life -- is one that is expected to engage the general public as well as the science community. To make the landing site data easily accessible and meaningful to the public, CMEX is planning to use the IHMC Cmap browser as its user interface.

An Integrated Human/Murine Transcriptome and Pathway Approach To Identify Prenatal Treatments For Down Syndrome.

PubMed

Guedj, Faycal; Pennings, Jeroen LA; Massingham, Lauren J; Wick, Heather C; Siegel, Ashley E; Tantravahi, Umadevi; Bianchi, Diana W

2016-09-02

Anatomical and functional brain abnormalities begin during fetal life in Down syndrome (DS). We hypothesize that novel prenatal treatments can be identified by targeting signaling pathways that are consistently perturbed in cell types/tissues obtained from human fetuses with DS and mouse embryos. We analyzed transcriptome data from fetuses with trisomy 21, age and sex-matched euploid controls, and embryonic day 15.5 forebrains from Ts1Cje, Ts65Dn, and Dp16 mice. The new datasets were compared to other publicly available datasets from humans with DS. We used the human Connectivity Map (CMap) database and created a murine adaptation to identify FDA-approved drugs that can rescue affected pathways. USP16 and TTC3 were dysregulated in all affected human cells and two mouse models. DS-associated pathway abnormalities were either the result of gene dosage specific effects or the consequence of a global cell stress response with activation of compensatory mechanisms. CMap analyses identified 56 molecules with high predictive scores to rescue abnormal gene expression in both species. Our novel integrated human/murine systems biology approach identified commonly dysregulated genes and pathways. This can help to prioritize therapeutic molecules on which to further test safety and efficacy. Additional studies in human cells are ongoing prior to pre-clinical prenatal treatment in mice.

Predicting protein contact map using evolutionary and physical constraints by integer programming.

PubMed

Wang, Zhiyong; Xu, Jinbo

2013-07-01

Protein contact map describes the pairwise spatial and functional relationship of residues in a protein and contains key information for protein 3D structure prediction. Although studied extensively, it remains challenging to predict contact map using only sequence information. Most existing methods predict the contact map matrix element-by-element, ignoring correlation among contacts and physical feasibility of the whole-contact map. A couple of recent methods predict contact map by using mutual information, taking into consideration contact correlation and enforcing a sparsity restraint, but these methods demand for a very large number of sequence homologs for the protein under consideration and the resultant contact map may be still physically infeasible. This article presents a novel method PhyCMAP for contact map prediction, integrating both evolutionary and physical restraints by machine learning and integer linear programming. The evolutionary restraints are much more informative than mutual information, and the physical restraints specify more concrete relationship among contacts than the sparsity restraint. As such, our method greatly reduces the solution space of the contact map matrix and, thus, significantly improves prediction accuracy. Experimental results confirm that PhyCMAP outperforms currently popular methods no matter how many sequence homologs are available for the protein under consideration. http://raptorx.uchicago.edu.

[A family with autosomal dominant temporal lobe epilepsy accompanied by motor and sensory neuropathy].

PubMed

Matsuoka, Takeshi; Furuya, Hirokazu; Ikezoe, Koji; Murai, Hiroyuki; Ohyagi, Yasumasa; Yoshiura, Takashi; Sasaki, Masayuki; Tobimatsu, Syozo; Kira, Jun-ichi

2004-01-01

We report a 20-year-old man with temporal lobe epilepsy (TLE) accompanied by hereditary motor and sensory neuropathy (HMSN). He had experienced complex partial seizures (CPS), which started with a nausea-like feeling, followed by loss of consciousness and automatism, since he was 6 years old. The frequency of attacks was at first decreased by phenytoin. However, attacks increased again when he was 18 years old. On admission, neurological examination showed mild weakness of the toes, pes cavus, hammer toe and mildly impaired vibratory sensation in his legs. Ten people in four generations of his family showed a history of epilepsy in the autosomal dominant inheritance form. His younger sister and mother had a history of epilepsy accompanied with pes cavus, hammer toe, weakness of toe and finger extension and mildly impaired vibratory sensation as well. Direct sequencing of the glioma-inactivated leucine-rich gene (LGI1), in which several mutations were reported in patients with familial lateral temporal lobe epilepsy, showed no specific mutation in this family. On consecutive video-EEG monitoring, paroxysmal rhythmic activity was confirmed in his left fronto-temporal region when he showed automatism, and then a generalized slow burst activity was detected when he lost consciousness. For his seizures, TLE with secondary generalization was diagnosed. In the nerve conduction study, delayed nerve conduction, distal motor latency and decreased amplitudes of the compound muscle action potentials (CMAP) of bilateral peroneal nerves were observed, indicating the existence of mild axonal degeneration. Based on these data, we consider that this family to be a new phenotype of autosomal dominant TLE accompanied by motor and sensory neuropathy.

MSCs ameliorates DPN induced cellular pathology via [Ca2+ ]i homeostasis and scavenging the pro-inflammatory cytokines.

PubMed

Chandramoorthy, Harish C; Bin-Jaliah, Ismaeel; Karari, Hussian; Rajagopalan, Prasanna; Ahmed Shariff, Mohammed Eajaz; Al-Hakami, Ahmed; Al-Humayad, Suliman M; Baptain, Fawzi A; Ahmed, Humeda Suekit; Yassin, Hanaa Z; Haidara, Mohamed A

2018-02-01

The MSCs of various origins are known to ameliorate or modulate cell survival strategies. We investigated, whether UCB MSCs could improve the survival of the human neuronal cells and/or fibroblast assaulted with DPN sera. The results showed, the co-culture of UCB MSCs with human neuronal cells and/or fibroblasts could effectively scavenge the pro-inflammatory cytokines TNF-α, IL-1β, IFN-ɤ and IL - 12 and control the pro-apoptotic expression of p53/Bax. Further co-culture of UCB MSCs have shown to induce anti-inflammatory cytokines like IL-4, IL-10 and TGF-β and anti-apoptotic Bclxl/Bcl2 expression in the DPN sera stressed cells. Amelioration of elevated [Ca 2+ ] i and cROS, the portent behind the NFκB/Caspase-3 mediated inflammation in DPN rescued the cells from apoptosis. The results of systemic administration of BM MSCs improved DPN pathology in rat as extrapolated from human cell model. The BM MSCs ameliorated prolonged distal motor latency (control: 0.70 ± 0.06, DPN: 1.29 ± 0.13 m/s DPN + BM MSCs: 0.89 ± 0.02 m/s, p < 0.05) and lowered high amplitude of compound muscle action potentials (CMAPs) (control: 12.36 ± 0.41, DPN: 7.52 ± 0.61 mV, DPN + MSCs: 8.79 ± 0.53 mV, p < 0.05), while slowly restoring the plasma glucose levels. Together, all these results showed that administration of BM or UCB MSCs improved the DPN via ameliorating pro-inflammatory cytokine signaling and [Ca 2+ ] i homeostasis. © 2017 Wiley Periodicals, Inc.

Changes and challenges: managing ADHD in a fast-paced world.

PubMed

Manos, Michael J; Tom-Revzon, Catherine; Bukstein, Oscar G; Crismon, M Lynn

2007-11-01

Attention-deficit/hyperactivity disorder (ADHD) impairs the lives of both children and adults. Undiagnosed and untreated, ADHD may have serious lifelong consequences. Research has identified diagnostic clues, neurotransmitter pathways, and psychiatric comorbidities related to ADHD, as well as effective pharmacologic, behavioral, and psychosocial interventions. Stimulant agents have been the foundation of ADHD therapy for more than 50 years. Availability of new extended-release (XR or ER) and longer-acting (LA) formulations and novel agents allows for wider and more individualized treatment choices. Side effects of stimulants are generally mild, short lived, and responsive to adjustments in dosage or timing. Outcomes in ADHD treatment can be improved with the use of clear treatment guidelines and tools to aid clinicians in implementing them efficiently and effectively. The Texas Children's Medication Algorithm Project (CMAP) provides a system of algorithm-driven treatment decisions that is evidence based and easy to implement. To (1) review the psychological components of attention, the neurotransmitter pathways associated with ADHD, and the array of therapeutic options for ADHD, with an emphasis on the most recent introductions to the therapeutic armamentarium; (2) discuss the rare psychiatric and cardiovascular side effects associated with stimulants; (3) review abuse liability, comorbidities, and suggested approaches to these issues; and (4) review the development and use of CMAP and offer resources for its implementation in clinical practice. The pathophysiology of ADHD is linked to dysfunction of fronto-subcortical networks and dysregulation of dopaminergic, noradrenergic, and nicotinic neurotransmitter systems. An additive effect of multiple genes as well as environmental influences contributes to the clinical picture. Treatment with stimulants and nonstimulants has proven effective in different subgroups, with the effectiveness of specific agents most likely related to the primary neurotransmitter involved. Availability of XR, ER, LA, and transdermal stimulant formulations, as well as alternative nonstimulant agents, offers new options for the pharmacotherapy of ADHD. Major concerns associated with abuse liability of stimulants have been allayed by the availability of ER formulations, which have reduced reinforcing effects associated with short-acting preparations. Medication outcomes in ADHD can be enhanced by the use of evidence-based algorithms such as CMAP. Keys to success are adequate initial assessment and diagnosis, the use of sustained-release products, sufficient dose titration, and the use of clinical rating scales with feedback from caregivers and teachers. Optimal treatment outcomes can be achieved by appropriate pharmacotherapy combined with psychosocial interventions.

Is the Conformational Ensemble of Alzheimer’s Aβ10-40 Peptide Force Field Dependent?

PubMed Central

Siwy, Christopher M.

2017-01-01

By applying REMD simulations we have performed comparative analysis of the conformational ensembles of amino-truncated Aβ10-40 peptide produced with five force fields, which combine four protein parameterizations (CHARMM36, CHARMM22*, CHARMM22/cmap, and OPLS-AA) and two water models (standard and modified TIP3P). Aβ10-40 conformations were analyzed by computing secondary structure, backbone fluctuations, tertiary interactions, and radius of gyration. We have also calculated Aβ10-40 3JHNHα-coupling and RDC constants and compared them with their experimental counterparts obtained for the full-length Aβ1-40 peptide. Our study led us to several conclusions. First, all force fields predict that Aβ adopts unfolded structure dominated by turn and random coil conformations. Second, specific TIP3P water model does not dramatically affect secondary or tertiary Aβ10-40 structure, albeit standard TIP3P model favors slightly more compact states. Third, although the secondary structures observed in CHARMM36 and CHARMM22/cmap simulations are qualitatively similar, their tertiary interactions show little consistency. Fourth, two force fields, OPLS-AA and CHARMM22* have unique features setting them apart from CHARMM36 or CHARMM22/cmap. OPLS-AA reveals moderate β-structure propensity coupled with extensive, but weak long-range tertiary interactions leading to Aβ collapsed conformations. CHARMM22* exhibits moderate helix propensity and generates multiple exceptionally stable long- and short-range interactions. Our investigation suggests that among all force fields CHARMM22* differs the most from CHARMM36. Fifth, the analysis of 3JHNHα-coupling and RDC constants based on CHARMM36 force field with standard TIP3P model led us to an unexpected finding that in silico Aβ10-40 and experimental Aβ1-40 constants are generally in better agreement than these quantities computed and measured for identical peptides, such as Aβ1-40 or Aβ1-42. This observation suggests that the differences in the conformational ensembles of Aβ10-40 and Aβ1-40 are small and the former can be used as proxy of the full-length peptide. Based on this argument, we concluded that CHARMM36 force field with standard TIP3P model produces the most accurate representation of Aβ10-40 conformational ensemble. PMID:28085875

Effects of Source-Apportioned Coarse Particulate Matter (PM) ...

EPA Pesticide Factsheets

The Cleveland Multiple Air Pollutant Study (CMAPS) is one of the first comprehensive studies conducted to evaluate particulate matter (PM) over local and regional scales. Cleveland and the nearby Ohio River Valley impart significant regional sources of air pollution including coal combustion and steel production. Size-fractionated PM (coarse, fine and ultrafine) were collected from an urban site (G.T. Craig (GTC)) and a rural site (Chippewa Lake monitor (CLM) located 53 km southwest of Cleveland) from July 2009 to June 2010. Following collection, resulting speciated PM data were apportioned to identify local industrial emission sources for each size fraction and location, indicating these samples were enriched with resident emission sources. This study was designed to determine whether exposure of the CMAPS coarse PM contributes to the exacerbation of allergic asthma. Non-sensitized and house dust mite (HDM)-sensitized female Balb/cJ mice (n= 8/group) were exposed via oropharyngeal (OP) aspiration to 100 g coarse fractions of one of five source apportioned groups representative of distinct time periods of 4-6 weeks (traffic, coal, steel 1, steel 2, or winter PM) and OP challenge with HDM conducted 2 hr following dosing with PM. Two days later, airway responsiveness to methacholine aerosol was assessed in anesthetized ventilated control and HDM mice. The HDM-allergic mice demonstrated increased airway reactivity in comparison to control mice. Bronchoalveolar l

Effects of different force fields on the structural character of α synuclein β-hairpin peptide (35-56) in aqueous environment.

PubMed

Kundu, Sangeeta

2018-02-01

The hallmark of Parkinson's disease (PD) is the intracellular protein aggregation forming Lewy Bodies (LB) and Lewy neuritis which comprise mostly of a protein, alpha synuclein (α-syn). Molecular dynamics (MD) simulation methods can augment experimental techniques to understand misfolding and aggregation pathways with atomistic resolution. The quality of MD simulations for proteins and peptides depends greatly on the accuracy of empirical force fields. The aim of this work is to investigate the effects of different force fields on the structural character of β hairpin fragment of α-syn (residues 35-56) peptide in aqueous solution. Six independent MD simulations are done in explicit solvent using, AMBER03, AMBER99SB, GROMOS96 43A1, GROMOS96 53A6, OPLS-AA, and CHARMM27 force fields with CMAP corrections. The performance of each force field is assessed from several structural parameters such as root mean square deviation (RMSD), root mean square fluctuation (RMSF), radius of gyration (Rg), solvent accessible surface area (SASA), formation of β-turn, the stability of folded β-hairpin structure, and the favourable conformations obtained for different force fields. In this study, CMAP correction of CHARMM27 force field is found to overestimate the helical conformation, while GROMOS96 53A6 is found to most successfully capture the conformational dynamics of α-syn β-hairpin fragment as elicited from NMR.

[Study on action mechanism and material base of compound Danshen dripping pills in treatment of carotid atherosclerosis based on techniques of gene expression profile and molecular fingerprint].

PubMed

Zhou, Wei; Song, Xiang-gang; Chen, Chao; Wang, Shu-mei; Liang, Sheng-wang

2015-08-01

Action mechanism and material base of compound Danshen dripping pills in treatment of carotid atherosclerosis were discussed based on gene expression profile and molecular fingerprint in this paper. First, gene expression profiles of atherosclerotic carotid artery tissues and histologically normal tissues in human body were collected, and were screened using significance analysis of microarray (SAM) to screen out differential gene expressions; then differential genes were analyzed by Gene Ontology (GO) analysis and KEGG pathway analysis; to avoid some genes with non-outstanding differential expression but biologically importance, Gene Set Enrichment Analysis (GSEA) were performed, and 7 chemical ingredients with higher negative enrichment score were obtained by Cmap method, implying that they could reversely regulate the gene expression profiles of pathological tissues; and last, based on the hypotheses that similar structures have similar activities, 336 ingredients of compound Danshen dripping pills were compared with 7 drug molecules in 2D molecular fingerprints method. The results showed that 147 differential genes including 60 up-regulated genes and 87 down regulated genes were screened out by SAM. And in GO analysis, Biological Process ( BP) is mainly concerned with biological adhesion, response to wounding and inflammatory response; Cellular Component (CC) is mainly concerned with extracellular region, extracellular space and plasma membrane; while Molecular Function (MF) is mainly concerned with antigen binding, metalloendopeptidase activity and peptide binding. KEGG pathway analysis is mainly concerned with JAK-STAT, RIG-I like receptor and PPAR signaling pathway. There were 10 compounds, such as hexadecane, with Tanimoto coefficients greater than 0.85, which implied that they may be the active ingredients (AIs) of compound Danshen dripping pills in treatment of carotid atherosclerosis (CAs). The present method can be applied to the research on material base and molecular action mechanism of TCM.

Variability of the recent climate of eastern Africa

NASA Astrophysics Data System (ADS)

Schreck, Carl J., III; Semazzi, Fredrick H. M.

2004-05-01

The primary objective of this study is to investigate the recent variability of the eastern African climate. The region of interest is also known as the Greater Horn of Africa (GHA), and comprises the countries of Burundi, Djibouti, Eritrea, Ethiopia, Kenya, Rwanda, Somalia, Sudan, Uganda, and Tanzania.The analysis was based primarily on the construction of empirical orthogonal functions (EOFs) of gauge rainfall data and on CPC Merged Analysis of Precipitation (CMAP) data, derived from a combination of rain-gauge observations and satellite estimates. The investigation is based on the period 1961-2001 for the short rains season of eastern Africa of October through to December. The EOF analysis was supplemented by projection of National Centers for Environmental Prediction wind data onto the rainfall eigenmodes to understand the rainfall-circulation relationships. Furthermore, correlation and composite analyses have been performed with the Climatic Research Unit globally averaged surface-temperature time series to explore the potential relationship between the climate of eastern Africa and global warming.The most dominant mode of variability (EOF1) based on CMAP data over eastern Africa corresponds to El Niño-southern oscillation (ENSO) climate variability. It is associated with above-normal rainfall amounts during the short rains throughout the entire region, except for Sudan. The corresponding anomalous low-level circulation is dominated by easterly inflow from the Indian Ocean, and to a lesser extent the Congo tropical rain forest, into the positive rainfall anomaly region that extends across most of eastern Africa. The easterly inflow into eastern Africa is part of diffluent outflow from the maritime continent during the warm ENSO events. The second eastern African EOF (trend mode) is associated with decadal variability. In distinct contrast from the ENSO mode pattern, the trend mode is characterized by positive rainfall anomalies over the northern sector of eastern Africa and opposite conditions over the southern sector. This rainfall trend mode eluded detection in previous studies that did not include recent decades of data, because the signal was still relatively weak. The wind projection onto this mode indicates that the primary flow that feeds the positive anomaly region over the northern part of eastern Africa emanates primarily from the rainfall-deficient southern region of eastern Africa and Sudan. Although we do not assign attribution of the trend mode to global warming (in part because of the relatively short period of analysis), the evidence, based on our results and previous studies, strongly suggests a potential connection.

Undergraduate otolaryngology education at the University of Toronto: a review using a curriculum mapping system.

PubMed

Oyewumi, Modupe; Isaac, Kathryn; Schreiber, Martin; Campisi, Paolo

2012-02-01

The aim of Canadian medical school curricula is to provide educational experiences that satisfy the specific objectives set out by the Medical Council of Canada. However, for specialties such as otolaryngology, there is considerable variability in student exposure to didactic and clinical teaching across Canadian medical schools, making it unclear whether students receive sufficient teaching of core otolaryngology content and clinical skills. The goal of this review was to assess the exposure to otolaryngology instruction in the undergraduate medical curriculum at the University of Toronto. Otolaryngology objectives were derived from objectives created by the Medical Council of Canada and the University of Toronto. The University of Toronto's recently developed Curriculum Mapping System (CMap) was used to perform a keyword search of otolaryngology objectives to establish when and to what extent essential topics were being taught. All (10 of 10) major topics and skills identified were covered in the undergraduate medical curriculum. Although no major gaps were identified, an uneven distribution of teaching time exists. The majority (> 90%) of otolaryngology education occurs during year 1 of clerkship. The amount of preclerkship education was extremely limited. Essential otolaryngology topics and skills are taught within the University of Toronto curriculum. The CMap was an effective tool to assess the otolaryngology curriculum and was able to identify gaps in otolaryngology education during the preclerkship years of medical school. As a result, modifications to the undergraduate curriculum have been implemented to provide additional teaching during the preclerkship years.

Cytoscape file of chemical networks

EPA Pesticide Factsheets

The maximum connectivity scores of pairwise chemical conditions summarized from Cmap results in a file with Cytoscape format (http://www.cytoscape.org/). The figures in the publication were generated from this file. The Cytoscape file is formed from importing the eight text file therein.This dataset is associated with the following publication:Wang , R., A. Biales , N. Garcia-Reyero, E. Perkins, D. Villeneuve, G. Ankley, and D. Bencic. Fish Connectivity Mapping: Linking Chemical Stressors by Their MOA-Driven Transcriptomic Profiles. BMC Genomics. BioMed Central Ltd, London, UK, 17(84): 1-20, (2016).

Cranial nerve monitoring during subpial dissection in temporomesial surgery.

PubMed

Ortler, Martin; Fiegele, Thomas; Walser, Gerald; Trinka, Eugen; Eisner, Wilhelm

2011-06-01

Cranial nerves (CNs) crossing between the brainstem and skull base at the level of the tentorial hiatus may be at risk in temporomesial surgery involving subpial dissection and/or tumorous growth leading to distorted anatomy. We aimed to identify the surgical steps most likely to result in CN damage in this type of surgery. Electromyographic responses obtained with standard neuromonitoring techniques and a continuous free-running EMG were graded as either contact activity or pathological spontaneous activity (PSA) during subpial resection of temporomesial structures in 16 selective amygdalohippocampectomy cases. Integrity of peripheral motor axons was tested by transpial/transarachnoidal electrical stimulation while recording compound muscle action potentials from distal muscle(s). Continuous EMG showed pathological activity in five (31.2%) patients. Nine events with PSA (slight activity, n = 8; strong temporary activity, n = 1) were recorded. The oculomotor nerve was involved three times, the trochlear nerve twice, the facial nerve once, and all monitored nerves on three occasions. Surgical maneuvers associated with PSA were the resection of deep parts of the hippocampus and parahippocampal gyrus (CN IV, twice; CN III, once), lining with or removing cotton patties from the resection cavity (III, twice; all channels, once) and indirect exertion of tension on the intact pia/arachnoid of the uncal region while mobilizing the hippocampus and parahippocampal gyrus en bloc (all channels, once; III, once). CMAPs were observed at 0.3 mA in two patients and at 0.6 mA in one patient, and without registering the exact amount of intensity in three patients. The most dangerous steps leading to cranial nerve damage during mesial temporal lobe surgery are the final stages of the intervention while the resection is being completed in the deep posterior part and the resection cavity is being lined with patties. Distant traction may act on nerves crossing the tentorial hiatus via the intact arachnoid.

Large-area irradiated low-level laser effect in a biodegradable nerve guide conduit on neural regeneration of peripheral nerve injury in rats.

PubMed

Shen, Chiung-Chyi; Yang, Yi-Chin; Liu, Bai-Shuan

2011-08-01

This study used a biodegradable composite containing genipin-cross-linked gelatin annexed with β-tricalcium phosphate ceramic particles (genipin-gelatin-tricalcium phosphate, GGT), developed in a previous study, as a nerve guide conduit. The aim of this study was to analyse the influence of a large-area irradiated aluminium-gallium-indium phosphide (AlGaInP) diode laser (660 nm) on the neural regeneration of the transected sciatic nerve after bridging the GGT nerve guide conduit in rats. The animals were divided into two groups: group 1 comprised sham-irradiated controls and group 2 rats underwent low-level laser (LLL) therapy. A compact multi-cluster laser system with 20 AlGaInP laser diodes (output power, 50mW) was applied transcutaneously to the injured peripheral nerve immediately after closing the wound, which was repeated daily for 5 min for 21 consecutive days. Eight weeks after implantation, walking track analysis showed a significantly higher sciatic function index (SFI) score (P<0.05) and better toe spreading development in the laser-treated group than in the sham-irradiated control group. For electrophysiological measurement, both the mean peak amplitude and nerve conduction velocity of compound muscle action potentials (CMAPs) were higher in the laser-treated group than in the sham-irradiated group. The two groups were found to be significantly different during the experimental period (P<0.005). Histomorphometric assessments revealed that the qualitative observation and quantitative analysis of the regenerated nerve tissue in the laser-treated group were superior to those of the sham-irradiated group. Thus, the motor functional, electrophysiologic and histomorphometric assessments demonstrate that LLL therapy can accelerate neural repair of the corresponding transected peripheral nerve after bridging the GGT nerve guide conduit in rats. Copyright © 2011 Elsevier Ltd. All rights reserved.

An Update on Oceanic Precipitation Rate and its Zonal Distribution in Light of Advanced Observations from Space

NASA Technical Reports Server (NTRS)

Behrangi, Ali; Stephens, Graeme; Adler, Robert F.; Huffman, George J.; Lambrigsten, Bjorn; Lebstock, Matthew

2014-01-01

This study contributes to the estimation of the global mean and zonal distribution of oceanic precipitation rate using complementary information from advanced precipitation measuring sensors and provides an independent reference to assess current precipitation products. Precipitation estimates from the Tropical Rainfall Measuring Mission (TRMM) precipitation radar (PR) and CloudSat cloud profiling radar (CPR) were merged, as the two complementary sensors yield an unprecedented range of sensitivity to quantify rainfall from drizzle through the most intense rates. At higher latitudes, where TRMM PR does not exist, precipitation estimates from Aqua's Advanced Microwave Scanning Radiometer for Earth Observing System (AMSR-E) complemented CloudSat CPR to capture intense precipitation rates. The high sensitivity of CPR allows estimation of snow rate, an important type of precipitation at high latitudes, not directly observed in current merged precipitation products. Using the merged precipitation estimate from the CloudSat, TRMM, and Aqua platforms (this estimate is abbreviated to MCTA), the authors' estimate for 3-yr (2007-09) nearglobal (80degS-80degN) oceanic mean precipitation rate is approx. 2.94mm/day. This new estimate of mean global ocean precipitation is about 9% higher than that of the corresponding Climate Prediction Center (CPC) Merged Analysis of Precipitation (CMAP) value (2.68mm/day) and about 4% higher than that of the Global Precipitation Climatology Project (GPCP; 2.82mm/day). Furthermore, MCTA suggests distinct differences in the zonal distribution of precipitation rate from that depicted in GPCPand CMAP, especially in the Southern Hemisphere.

Comparative Study of the Energetics of Ion Permeation in Kv1.2 and KcsA Potassium Channels

PubMed Central

Baştuğ, Turgut; Kuyucak, Serdar

2011-01-01

Biological ion channels rely on a multi-ion transport mechanism for fast yet selective permeation of ions. The crystal structure of the KcsA potassium channel provided the first microscopic picture of this process. A similar mechanism is assumed to operate in all potassium channels, but the validity of this assumption has not been well investigated. Here, we examine the energetics of ion permeation in Shaker Kv1.2 and KcsA channels, which exemplify the six-transmembrane voltage-gated and two-transmembrane inward-rectifier channels. We study the feasibility of binding a third ion to the filter and the concerted motion of ions in the channel by constructing the potential of mean force for K+ ions in various configurations. For both channels, we find that a pair of K+ ions can move almost freely within the filter, but a relatively large free-energy barrier hinders the K+ ion from stepping outside the filter. We discuss the effect of the CMAP dihedral energy correction that was recently incorporated into the CHARMM force field on ion permeation dynamics. PMID:21281577

Reviews

NASA Astrophysics Data System (ADS)

2007-09-01

WE RECOMMEND Energy Foresight Valuable and original GCSE curriculum support on DVD Developing Scientific Literacy: Using News Media in the Classroom This book helpfully evaluates science stories in today's media Radioactivity Explained and Electricity Explained Interactive software ideal for classroom use TEP Generator Wind-up generator specially designed for schools SEP Energymeter A joule meter with more uses than its appearance suggests Into the Cool: Energy Flow, Thermodynamics and Life This book explores the physics behind biology CmapTools Handy software for mapping knowledge and resources LogIT Black Box This hub contains multiple sensors for endless experimental fun WEB WATCH Water Web 2.0

Gene expression-based chemical genomics identifies potential therapeutic drugs in hepatocellular carcinoma.

PubMed

Chen, Ming-Huang; Yang, Wu-Lung R; Lin, Kuan-Ting; Liu, Chia-Hung; Liu, Yu-Wen; Huang, Kai-Wen; Chang, Peter Mu-Hsin; Lai, Jin-Mei; Hsu, Chun-Nan; Chao, Kun-Mao; Kao, Cheng-Yan; Huang, Chi-Ying F

2011-01-01

Hepatocellular carcinoma (HCC) is an aggressive tumor with a poor prognosis. Currently, only sorafenib is approved by the FDA for advanced HCC treatment; therefore, there is an urgent need to discover candidate therapeutic drugs for HCC. We hypothesized that if a drug signature could reverse, at least in part, the gene expression signature of HCC, it might have the potential to inhibit HCC-related pathways and thereby treat HCC. To test this hypothesis, we first built an integrative platform, the "Encyclopedia of Hepatocellular Carcinoma genes Online 2", dubbed EHCO2, to systematically collect, organize and compare the publicly available data from HCC studies. The resulting collection includes a total of 4,020 genes. To systematically query the Connectivity Map (CMap), which includes 6,100 drug-mediated expression profiles, we further designed various gene signature selection and enrichment methods, including a randomization technique, majority vote, and clique analysis. Subsequently, 28 out of 50 prioritized drugs, including tanespimycin, trichostatin A, thioguanosine, and several anti-psychotic drugs with anti-tumor activities, were validated via MTT cell viability assays and clonogenic assays in HCC cell lines. To accelerate their future clinical use, possibly through drug-repurposing, we selected two well-established drugs to test in mice, chlorpromazine and trifluoperazine. Both drugs inhibited orthotopic liver tumor growth. In conclusion, we successfully discovered and validated existing drugs for potential HCC therapeutic use with the pipeline of Connectivity Map analysis and lab verification, thereby suggesting the usefulness of this procedure to accelerate drug repurposing for HCC treatment.

Spatial extent of potential habitats of the Mesophotic Coral Ecosystem (MCE, 20-80 m) in the tropical North Atlantic (TNA)

NASA Astrophysics Data System (ADS)

Ginsburg, R. N.

2012-12-01

The Mesophotic Coral Ecosystem is the deeper-water extension of the much-studied, shallow reef community. It occurs on steep slopes and shelf areas, in the TNA off Belize, the Bahamas, the US Virgin Islands, and the Flower Garden Banks. Framework-building corals at these depths are primarily platy montastraeids and agariciids, with lesser amounts of massive encrusting species. The closely-spaced, platy colonies, expanding up to nearly two meters in diameter have up to 50% live coral cover. The colonies are elevated above the substrate. Their growth creates a thicket-like structure with large, open spaces for mobile species (fish and crustaceans) and extensive habitat for attached and grazing invertebrates. The MCE includes genera or species of zooxanthellate corals, invertebrates and fish, some of which are the same as those in shallow water. Given, the widespread, recent declines of TNA coral communities at depth less than 20 m, it is essential to know the total regional extent of the MCE. To determine the likely depth locations of these deeper coral communities we used methods pioneered by REEFS AT RISK,1998 that incorporates data from the Danish Hydrological Institute (DHI), "MIKE C-MAP" depth points and data on coastline location *NASA, "Sea WiFS" and NIMA, "VMAP," 1997. The results for the larger areas of reef development and for shelf areas are below:Potential MCE shelf habitats.t; Potential MCE platform margin habitats.t;

Neuromuscular Functions on Experimental Acute Methanol Intoxication.

PubMed

Moral, Ali Reşat; Çankayalı, İlkin; Sergin, Demet; Boyacılar, Özden

2015-10-01

The incidence of accidental or suicidal ingestion of methyl alcohol is high and methyl alcohol intoxication has high mortality. Methyl alcohol intoxication causes severe neurological sequelae and appears to be a significant problem. Methyl alcohol causes acute metabolic acidosis, optic neuropathy leading to permanent blindness, respiratory failure, circulatory failure and death. It is metabolised in the liver, and its metabolite formic acid has direct toxic effects, causing oxidative stress, mitochondrial damage and increased lipid peroxidation associated with the mechanism of neurotoxicity. Methanol is known to cause acute toxicity of the central nervous system; however, the effects on peripheral neuromuscular transmission are unknown. In our study, we aimed to investigate the electrophysiological effects of experimentally induced acute methanol intoxication on neuromuscular transmission in the early period (first 24 h). After approval by the Animal Experiment Ethics Committee of Ege University, the study was carried out on 10 Wistar rats, each weighing about 200 g. During electrophysiological recordings and orogastric tube insertion, the rats were anaesthetised using intra-peritoneal (IP) injection of ketamine 100 mg kg(-1) and IP injection of xylazine 10 mg kg(-1). The rats were given 3 g kg(-1) methyl alcohol by the orogastric tube. Electrophysiological measurements from the gastrocnemius muscle were compared with baseline. Latency measurements before and 24 h after methanol injection were 0.81±0.11 ms and 0.76±0.12 ms, respectively. CMAP amplitude measurements before and 24 h after methanol injection were 9.85±0.98 mV and 9.99±0.40 mV, respectively. CMAP duration measurements before and 24 h after methanol injection were 9.86±0.03 ms and 9.86±0.045 ms, respectively. It was concluded that experimental methanol intoxication in the acute phase (first 24 h) did not affect neuromuscular function.

Phrenic Nerve Conduction Study in the Early Stage of Guillain-Barre Syndrome as a Predictor of Respiratory Failure.

PubMed

Sen, Barun Kumar; Pandit, Alak

2018-01-01

Guillain-Barré syndrome (GBS) has unpredictable clinical course with severe complication of respiratory failure. To identify clinical profiles and electrophysiological study particularly non-invasive Phrenic nerve conduction study in patients of early GBS to predict respiratory failure. 64 adult (age≥18yrs) patients of early GBS (onset ≤ 14 days) during the study period from January 2014 to October 2015 were evaluated by clinical profiles of age, gender, antecedent infection, time to peak disability, single breath counts, cranial nerve involvement, autonomic dysfunction and non-invasive Phrenic nerve conduction study. Patients with predisposition factors of polyneuropathy like diabetes mellitus, hypothyroidism, vitamin deficiency, renal failure were excluded. Among 64 patients abnormal phrenic nerve conduction study was seen in 65.62% cases (42/64) and 45.23% (19/42) of them developed respiratory failure. Phrenic nerve sum latency, amplitude, duration and area were abnormal in those who developed respiratory failure and they had sum of phrenic nerve latency >28 msec, sum of CMAP amplitude <300 μV, sum of CMAP duration >50 msec and sum of area < 4 mVmS. None with normal phrenic nerve study developed respiratory failure. It was found that age, gender, preceding infection, autonomic involvement and types of GB syndrome had no influence on development of respiratory failure (p>0.05). Rapid disease progression to peak disability, more severe disease, shorter single breath counts and cranial nerve involvement were seen more often in patients with respiratory failure. Abnormal Phrenic nerve conduction study in the early Guillain-Barré syndrome might be of great value independently in predicting impending respiratory failure.

Phrenic Nerve Conduction Study in the Early Stage of Guillain–Barre Syndrome as a Predictor of Respiratory Failure

PubMed Central

Sen, Barun Kumar; Pandit, Alak

2018-01-01

Background: Guillain-Barré syndrome (GBS) has unpredictable clinical course with severe complication of respiratory failure. Objective: To identify clinical profiles and electrophysiological study particularly non-invasive Phrenic nerve conduction study in patients of early GBS to predict respiratory failure. Methods: 64 adult (age≥18yrs) patients of early GBS (onset ≤ 14 days) during the study period from January 2014 to October 2015 were evaluated by clinical profiles of age, gender, antecedent infection, time to peak disability, single breath counts, cranial nerve involvement, autonomic dysfunction and non-invasive Phrenic nerve conduction study. Patients with predisposition factors of polyneuropathy like diabetes mellitus, hypothyroidism, vitamin deficiency, renal failure were excluded. Results: Among 64 patients abnormal phrenic nerve conduction study was seen in 65.62% cases (42/64) and 45.23% (19/42) of them developed respiratory failure. Phrenic nerve sum latency, amplitude, duration and area were abnormal in those who developed respiratory failure and they had sum of phrenic nerve latency >28 msec, sum of CMAP amplitude <300 μV, sum of CMAP duration >50 msec and sum of area < 4 mVmS. None with normal phrenic nerve study developed respiratory failure. It was found that age, gender, preceding infection, autonomic involvement and types of GB syndrome had no influence on development of respiratory failure (p>0.05). Rapid disease progression to peak disability, more severe disease, shorter single breath counts and cranial nerve involvement were seen more often in patients with respiratory failure. Conclusion: Abnormal Phrenic nerve conduction study in the early Guillain-Barré syndrome might be of great value independently in predicting impending respiratory failure. PMID:29720799

Sensorimotor Peripheral Nerve Function and Physical Activity in Older Men

PubMed Central

Lange-Maia, Brittney S.; Cauley, Jane A.; Newman, Anne B.; Boudreau, Robert M.; Jakicic, John M.; Glynn, Nancy W.; Zivkovic, Sasa; Dam, Tien; Caserotti, Paolo; Cawthon, Peggy M.; Orwoll, Eric S.; Strotmeyer, Elsa S.

2017-01-01

We determined whether sensorimotor peripheral nerve (PN) function was associated with physical activity (PA) in older men. The Osteoporotic Fractures in Men Study Pittsburgh, PA, site (n=328, age 78.8±4.7 years), conducted PN testing, including: peroneal motor and sural sensory nerve conduction (latencies, amplitudes: CMAP and SNAP for motor and sensory amplitude, respectively), 1.4g/10g monofilament (dorsum of the great toe), and neuropathy symptoms. ANOVA and multivariate linear regression modeled PN associations with PA (Physical Activity Scale for the Elderly (PASE) and SenseWear Armband). After multivariable adjustment, better motor latency was associated with higher PASE scores (160.5±4.8 vs 135.6±6.7, p<0.01). Those without vs. with neuropathy symptoms had higher PASE scores (157.6±5.3 vs 132.9±7.1, p<0.01). Better vs. worse SNAP was associated with slightly more daily vigorous activity (9.5±0.8 vs. 7.3±0.7, p=0.05). Other PN measures were not associated with PA. Certain PN measures were associated with lower PA, suggesting a potential pathway for disability. PMID:26964668

Pharmacogenomic identification of small molecules for lineage specific manipulation of subventricular zone germinal activity.

PubMed

Azim, Kasum; Angonin, Diane; Marcy, Guillaume; Pieropan, Francesca; Rivera, Andrea; Donega, Vanessa; Cantù, Claudio; Williams, Gareth; Berninger, Benedikt; Butt, Arthur M; Raineteau, Olivier

2017-03-01

Strategies for promoting neural regeneration are hindered by the difficulty of manipulating desired neural fates in the brain without complex genetic methods. The subventricular zone (SVZ) is the largest germinal zone of the forebrain and is responsible for the lifelong generation of interneuron subtypes and oligodendrocytes. Here, we have performed a bioinformatics analysis of the transcriptome of dorsal and lateral SVZ in early postnatal mice, including neural stem cells (NSCs) and their immediate progenies, which generate distinct neural lineages. We identified multiple signaling pathways that trigger distinct downstream transcriptional networks to regulate the diversity of neural cells originating from the SVZ. Next, we used a novel in silico genomic analysis, searchable platform-independent expression database/connectivity map (SPIED/CMAP), to generate a catalogue of small molecules that can be used to manipulate SVZ microdomain-specific lineages. Finally, we demonstrate that compounds identified in this analysis promote the generation of specific cell lineages from NSCs in vivo, during postnatal life and adulthood, as well as in regenerative contexts. This study unravels new strategies for using small bioactive molecules to direct germinal activity in the SVZ, which has therapeutic potential in neurodegenerative diseases.

A Chemocentric Informatics Approach to Drug Discovery: Identification and Experimental Validation of Selective Estrogen Receptor Modulators as ligands of 5-Hydroxytryptamine-6 Receptors and as Potential Cognition Enhancers

PubMed Central

Hajjo, Rima; Setola, Vincent; Roth, Bryan L.; Tropsha, Alexander

2012-01-01

We have devised a chemocentric informatics methodology for drug discovery integrating independent approaches to mining biomolecular databases. As a proof of concept, we have searched for novel putative cognition enhancers. First, we generated Quantitative Structure- Activity Relationship (QSAR) models of compounds binding to 5-hydroxytryptamine-6 receptor (5HT6R), a known target for cognition enhancers, and employed these models for virtual screening to identify putative 5-HT6R actives. Second, we queried chemogenomics data from the Connectivity Map (http://www.broad.mit.edu/cmap/) with the gene expression profile signatures of Alzheimer’s disease patients to identify compounds putatively linked to the disease. Thirteen common hits were tested in 5-HT6R radioligand binding assays and ten were confirmed as actives. Four of them were known selective estrogen receptor modulators that were never reported as 5-HT6R ligands. Furthermore, nine of the confirmed actives were reported elsewhere to have memory-enhancing effects. The approaches discussed herein can be used broadly to identify novel drug-target-disease associations. PMID:22537153

Application of Observed Precipitation in NCEP Global and Regional Data Assimilation Systems, Including Reanalysis and Land Data Assimilation

NASA Astrophysics Data System (ADS)

Mitchell, K. E.

2006-12-01

The Environmental Modeling Center (EMC) of the National Centers for Environmental Prediction (NCEP) applies several different analyses of observed precipitation in both the data assimilation and validation components of NCEP's global and regional numerical weather and climate prediction/analysis systems (including in NCEP global and regional reanalysis). This invited talk will survey these data assimilation and validation applications and methodologies, as well as the temporal frequency, spatial domains, spatial resolution, data sources, data density and data quality control in the precipitation analyses that are applied. Some of the precipitation analyses applied by EMC are produced by NCEP's Climate Prediction Center (CPC), while others are produced by the River Forecast Centers (RFCs) of the National Weather Service (NWS), or by automated algorithms of the NWS WSR-88D Radar Product Generator (RPG). Depending on the specific type of application in data assimilation or model forecast validation, the temporal resolution of the precipitation analyses may be hourly, daily, or pentad (5-day) and the domain may be global, continental U.S. (CONUS), or Mexico. The data sources for precipitation include ground-based gauge observations, radar-based estimates, and satellite-based estimates. The precipitation analyses over the CONUS are analyses of either hourly, daily or monthly totals of precipitation, and they are of two distinct types: gauge-only or primarily radar-estimated. The gauge-only CONUS analysis of daily precipitation utilizes an orographic-adjustment technique (based on the well-known PRISM precipitation climatology of Oregon State University) developed by the NWS Office of Hydrologic Development (OHD). The primary NCEP global precipitation analysis is the pentad CPC Merged Analysis of Precipitation (CMAP), which blends both gauge observations and satellite estimates. The presentation will include a brief comparison between the CMAP analysis and other global precipitation analyses by other institutions. Other global precipitation analyses produced by other methodologies are also used by EMC in certain applications, such as CPC's well-known satellite-IR based technique known as "GPI", and satellite-microwave based estimates from NESDIS or NASA. Finally, the presentation will cover the three assimilation methods used by EMC to assimilate precipitation data, including 1) 3D-VAR variational assimilation in NCEP's Global Data Assimilation System (GDAS), 2) direct insertion of precipitation-inferred vertical latent heating profiles in NCEP's N. American Data Assimilation System (NDAS) and its N. American Regional Reanalysis (NARR) counterpart, and 3) direct use of observed precipitation to drive the Noah land model component of NCEP's Global and N. American Land Data Assimilation Systems (GLDAS and NLDAS). In the applications of precipitation analyses in data assimilation at NCEP, the analyses are temporally disaggregated to hourly or less using time-weights calculated from A) either radar-based estimates or an analysis of hourly gauge-observations for the CONUS-domain daily precipitation analyses, or B) global model forecasts of 6-hourly precipitation (followed by linear interpolation to hourly or less) for the global CMAP precipitation analysis.

KSC History Project

NASA Technical Reports Server (NTRS)

Moore, Patrick K.

2002-01-01

The 2002 NASA/ASEE KSC History Project focused on a series of seven history initiatives designed to acquire, preserve, and interpret the history of Kennedy Space Center. These seven projects included the co-authoring of Voices From the Cape, historical work with NASA historian Roger Launius, the completion of a series of oral histories with key KSC personnel, a monograph on Public Affairs, the development of a Historical Concept Map (CMap) for history knowledge preservation, advice on KSC history database and web interface capabilities, the development of a KSC oral history program and guidelines of training and collection, and the development of collaborative relationships between Kennedy Space Center, the University of West Florida, and the University of Central Florida.

Novel SSR Markers from BAC-End Sequences, DArT Arrays and a Comprehensive Genetic Map with 1,291 Marker Loci for Chickpea (Cicer arietinum L.)

PubMed Central

Nayak, Spurthi N.; Varghese, Nicy; Shah, Trushar M.; Penmetsa, R. Varma; Thirunavukkarasu, Nepolean; Gudipati, Srivani; Gaur, Pooran M.; Kulwal, Pawan L.; Upadhyaya, Hari D.; KaviKishor, Polavarapu B.; Winter, Peter; Kahl, Günter; Town, Christopher D.; Kilian, Andrzej; Cook, Douglas R.; Varshney, Rajeev K.

2011-01-01

Chickpea (Cicer arietinum L.) is the third most important cool season food legume, cultivated in arid and semi-arid regions of the world. The goal of this study was to develop novel molecular markers such as microsatellite or simple sequence repeat (SSR) markers from bacterial artificial chromosome (BAC)-end sequences (BESs) and diversity arrays technology (DArT) markers, and to construct a high-density genetic map based on recombinant inbred line (RIL) population ICC 4958 (C. arietinum)×PI 489777 (C. reticulatum). A BAC-library comprising 55,680 clones was constructed and 46,270 BESs were generated. Mining of these BESs provided 6,845 SSRs, and primer pairs were designed for 1,344 SSRs. In parallel, DArT arrays with ca. 15,000 clones were developed, and 5,397 clones were found polymorphic among 94 genotypes tested. Screening of newly developed BES-SSR markers and DArT arrays on the parental genotypes of the RIL mapping population showed polymorphism with 253 BES-SSR markers and 675 DArT markers. Segregation data obtained for these polymorphic markers and 494 markers data compiled from published reports or collaborators were used for constructing the genetic map. As a result, a comprehensive genetic map comprising 1,291 markers on eight linkage groups (LGs) spanning a total of 845.56 cM distance was developed (http://cmap.icrisat.ac.in/cmap/sm/cp/thudi/). The number of markers per linkage group ranged from 68 (LG 8) to 218 (LG 3) with an average inter-marker distance of 0.65 cM. While the developed resource of molecular markers will be useful for genetic diversity, genetic mapping and molecular breeding applications, the comprehensive genetic map with integrated BES-SSR markers will facilitate its anchoring to the physical map (under construction) to accelerate map-based cloning of genes in chickpea and comparative genome evolution studies in legumes. PMID:22102885

Status of High Latitude Precipitation Estimates from Observations and Reanalyses

NASA Technical Reports Server (NTRS)

Behrangi, Ali; Christensen, Matthew; Richardson, Mark; Lebsock, Matthew; Stephens, Graeme; Huffman, George J.; Bolvin, David T.; Adler, Robert F.; Gardner, Alex; Lambrigtsen, Bjorn H.;

Analysis of Multiple Precipitation Products and Preliminary Assessment of Their Impact on Global Land Data Assimilation System (GLDAS) Land Surface States

NASA Technical Reports Server (NTRS)

Gottschalck, Jon; Meng, Jesse; Rodel, Matt; Houser, paul

2005-01-01

Land surface models (LSMs) are computer programs, similar to weather and climate prediction models, which simulate the stocks and fluxes of water (including soil moisture, snow, evaporation, and runoff) and energy (including the temperature of and sensible heat released from the soil) after they arrive on the land surface as precipitation and sunlight. It is not currently possible to measure all of the variables of interest everywhere on Earth with sufficient accuracy and space-time resolution. Hence LSMs have been developed to integrate the available observations with our understanding of the physical processes involved, using powerful computers, in order to map these stocks and fluxes as they change in time. The maps are used to improve weather forecasts, support water resources and agricultural applications, and study the Earth's water cycle and climate variability. NASA's Global Land Data Assimilation System (GLDAS) project facilitates testing of several different LSMs with a variety of input datasets (e.g., precipitation, plant type). Precipitation is arguably the most important input to LSMs. Many precipitation datasets have been produced using satellite and rain gauge observations and weather forecast models. In this study, seven different global precipitation datasets were evaluated over the United States, where dense rain gauge networks contribute to reliable precipitation maps. We then used the seven datasets as inputs to GLDAS simulations, so that we could diagnose their impacts on output stocks and fluxes of water. In terms of totals, the Climate Prediction Center (CPC) Merged Analysis of Precipitation (CMAP) had the closest agreement with the US rain gauge dataset for all seasons except winter. The CMAP precipitation was also the most closely correlated in time with the rain gauge data during spring, fall, and winter, while the satellitebased estimates performed best in summer. The GLDAS simulations revealed that modeled soil moisture is highly sensitive to precipitation, with differences in spring and summer as large as 45% depending on the choice of precipitation input.

Connectivity map identifies HDAC inhibition as a treatment option of high-risk hepatoblastoma.

PubMed

Beck, Alexander; Eberherr, Corinna; Hagemann, Michaela; Cairo, Stefano; Häberle, Beate; Vokuhl, Christian; von Schweinitz, Dietrich; Kappler, Roland

2016-11-01

Hepatoblastoma (HB) is the most common liver tumor of childhood, usually occurring in children under the age of 3 y. The prognosis of patients presenting with distant metastasis, vascular invasion and advanced tumor stages remains poor and children that do survive often face severe late effects from the aggressive chemotherapy regimen. To identify potential new therapeutics for high risk HB we used a 1,000-gene expression signature as input for a Connectivity Map (CMap) analysis, which predicted histone deacetylase (HDAC) inhibitors as a promising therapy option. Subsequent expression analysis of primary HB and HB cell lines revealed a general overexpression of HDAC1 and HDAC2, which has been suggested to be predictive for the efficacy of HDAC inhibition. Accordingly, treatment of HB cells with the HDAC inhibitors SAHA and MC1568 resulted in a potent reduction of cell viability, induction of apoptosis, reactivation of epigenetically suppressed tumor suppressor genes, and the reversion of the 16-gene HB classifier toward the more favorable expression signature. Most importantly, the combination of HDAC inhibitors and cisplatin - a major chemotherapeutic agent of HB treatment - revealed a strong synergistic effect, even at significantly reduced doses of cisplatin. Our findings suggest that HDAC inhibitors skew HB cells toward a more favorable prognostic phenotype through changes in gene expression, thus indicating a targeted molecular mechanism that seems to enhance the anti-proliferative effects of conventional chemotherapy. Thus, adding HDAC inhibitors to the treatment regimen of high risk HB could potentially improve outcomes and reduce severe late effects.

Concept Maps Applied to Mars Exploration Public Outreach

NASA Technical Reports Server (NTRS)

Briggs, Geoffrey; Canas, Alberto; Shamma, David; Scargle, Jeffrey; Novak, Joseph

2004-01-01

This paper describes CMEX Mars, an effort in the creation of a comprehensive set of concept maps to describe all aspects of Mars exploration. These concept maps, created using the CmapTools software developed by the Institute for Human and Machine Cognition, are available on the Internet at http:/cmex.arc.nasa.gov/CMEX and are linked among themselves as well as to resources on the Internet. The work described took place mainly between 1998 and 2001 and combined the goals of: 1) developing a library of concept maps for educational outreach while also 2) refining the capabilities of the software used to create the interactive maps and 3) making them available on the Internet. Here we focus on the library of Mars exploration concept maps that has been created.

KSC History Project

NASA Technical Reports Server (NTRS)

Moore, Patrick K.

2003-01-01

The 2003 NASA/ASEE KSC History Project focused on a series of six history initiatives designed to acquire, preserve, and interpret the history of Kennedy Space Center. These six projects included the completion of Voices From the Cape, historical work co-authored with NASA historian Roger Launius, the completion of a series of oral histories with key KSC personnel, expansion of monograph on Public Affairs into two comprehensive pieces on KSC press operations and KSC visitor operations, the expansion of KSC Historical Concept Maps (Cmap) for history knowledge preservation, the expansion of the KSC oral history program through the administration of an oral history workshop for KSC-based practitioners, and the continued collaborative relationships between Kennedy Space Center, the University of West Florida, the University of Central Florida and other institutions including the University of Louisiana at Lafayette.

Next-generation text-mining mediated generation of chemical response-specific gene sets for interpretation of gene expression data.

PubMed

Hettne, Kristina M; Boorsma, André; van Dartel, Dorien A M; Goeman, Jelle J; de Jong, Esther; Piersma, Aldert H; Stierum, Rob H; Kleinjans, Jos C; Kors, Jan A

2013-01-29

Availability of chemical response-specific lists of genes (gene sets) for pharmacological and/or toxic effect prediction for compounds is limited. We hypothesize that more gene sets can be created by next-generation text mining (next-gen TM), and that these can be used with gene set analysis (GSA) methods for chemical treatment identification, for pharmacological mechanism elucidation, and for comparing compound toxicity profiles. We created 30,211 chemical response-specific gene sets for human and mouse by next-gen TM, and derived 1,189 (human) and 588 (mouse) gene sets from the Comparative Toxicogenomics Database (CTD). We tested for significant differential expression (SDE) (false discovery rate -corrected p-values < 0.05) of the next-gen TM-derived gene sets and the CTD-derived gene sets in gene expression (GE) data sets of five chemicals (from experimental models). We tested for SDE of gene sets for six fibrates in a peroxisome proliferator-activated receptor alpha (PPARA) knock-out GE dataset and compared to results from the Connectivity Map. We tested for SDE of 319 next-gen TM-derived gene sets for environmental toxicants in three GE data sets of triazoles, and tested for SDE of 442 gene sets associated with embryonic structures. We compared the gene sets to triazole effects seen in the Whole Embryo Culture (WEC), and used principal component analysis (PCA) to discriminate triazoles from other chemicals. Next-gen TM-derived gene sets matching the chemical treatment were significantly altered in three GE data sets, and the corresponding CTD-derived gene sets were significantly altered in five GE data sets. Six next-gen TM-derived and four CTD-derived fibrate gene sets were significantly altered in the PPARA knock-out GE dataset. None of the fibrate signatures in cMap scored significant against the PPARA GE signature. 33 environmental toxicant gene sets were significantly altered in the triazole GE data sets. 21 of these toxicants had a similar toxicity pattern as the triazoles. We confirmed embryotoxic effects, and discriminated triazoles from other chemicals. Gene set analysis with next-gen TM-derived chemical response-specific gene sets is a scalable method for identifying similarities in gene responses to other chemicals, from which one may infer potential mode of action and/or toxic effect.

Next-generation text-mining mediated generation of chemical response-specific gene sets for interpretation of gene expression data

PubMed Central

2013-01-01

Background Availability of chemical response-specific lists of genes (gene sets) for pharmacological and/or toxic effect prediction for compounds is limited. We hypothesize that more gene sets can be created by next-generation text mining (next-gen TM), and that these can be used with gene set analysis (GSA) methods for chemical treatment identification, for pharmacological mechanism elucidation, and for comparing compound toxicity profiles. Methods We created 30,211 chemical response-specific gene sets for human and mouse by next-gen TM, and derived 1,189 (human) and 588 (mouse) gene sets from the Comparative Toxicogenomics Database (CTD). We tested for significant differential expression (SDE) (false discovery rate -corrected p-values < 0.05) of the next-gen TM-derived gene sets and the CTD-derived gene sets in gene expression (GE) data sets of five chemicals (from experimental models). We tested for SDE of gene sets for six fibrates in a peroxisome proliferator-activated receptor alpha (PPARA) knock-out GE dataset and compared to results from the Connectivity Map. We tested for SDE of 319 next-gen TM-derived gene sets for environmental toxicants in three GE data sets of triazoles, and tested for SDE of 442 gene sets associated with embryonic structures. We compared the gene sets to triazole effects seen in the Whole Embryo Culture (WEC), and used principal component analysis (PCA) to discriminate triazoles from other chemicals. Results Next-gen TM-derived gene sets matching the chemical treatment were significantly altered in three GE data sets, and the corresponding CTD-derived gene sets were significantly altered in five GE data sets. Six next-gen TM-derived and four CTD-derived fibrate gene sets were significantly altered in the PPARA knock-out GE dataset. None of the fibrate signatures in cMap scored significant against the PPARA GE signature. 33 environmental toxicant gene sets were significantly altered in the triazole GE data sets. 21 of these toxicants had a similar toxicity pattern as the triazoles. We confirmed embryotoxic effects, and discriminated triazoles from other chemicals. Conclusions Gene set analysis with next-gen TM-derived chemical response-specific gene sets is a scalable method for identifying similarities in gene responses to other chemicals, from which one may infer potential mode of action and/or toxic effect. PMID:23356878

Recent Precipitation Trends Over the Southern Ocean in Relation to Oceanic Freshening Near Antarctica

NASA Astrophysics Data System (ADS)

Cullather, R. I.; Jacobs, S. S.; Giulivi, C. F.; Leonard, K. C.; Stammerjohn, S. E.

2008-12-01

Quantitative assessments of large-scale precipitation over the world's oceanic regions are problematic, particularly for significant regions of the data-sparse Southern Hemisphere. Available data sets are based on the assimilation of land-based measurements, satellite radiance values, numerical weather forecast models, or some combination of the three. In this study we examine several products that cover most or all of the satellite era 1979-2007 over the Southern Ocean and surrounding mid-latitudes to 45°S. These include CMAP, the NCEP Reanalysis II, ERA-40, GPCP version 2, and the Japanese Re-analysis. Averaged fields from these data show large discrepancies in the mean spatial depiction and the annual cycle. Comparisons with unique in situ snowfall measurements and satellite-derived accumulation on sea ice are presented. The available record of oceanographic measurements in the Ross Sea indicates that salinity below 200 m in the Ross Sea has decreased by 0.03 per decade since 1958, with the highest (lowest) values in 1967 (2000). The fields examined here suggest that precipitation is likely not directly influencing the oceanic freshening observed in the Ross Sea, or in other coastal seas adjacent to Antarctica. The salinity anomaly is consistent with increasing attrition of continental ice, but places a heavy demand on the melt rate. Potential contributions to oceanic freshening from changes in sea ice extent, transport, and thickness are discussed.

Secondary Structure of Rat and Human Amylin across Force Fields

PubMed Central

Hoffmann, Kyle Quynn; McGovern, Michael; Chiu, Chi-cheng; de Pablo, Juan J.

2015-01-01

The aggregation of human amylin has been strongly implicated in the progression of Type II diabetes. This 37-residue peptide forms a variety of secondary structures, including random coils, α-helices, and β-hairpins. The balance between these structures depends on the chemical environment, making amylin an ideal candidate to examine inherent biases in force fields. Rat amylin differs from human amylin by only 6 residues; however, it does not form fibrils. Therefore it provides a useful complement to human amylin in studies of the key events along the aggregation pathway. In this work, the free energy of rat and human amylin was determined as a function of α-helix and β-hairpin content for the Gromos96 53a6, OPLS-AA/L, CHARMM22/CMAP, CHARMM22*, Amberff99sb*-ILDN, and Amberff03w force fields using advanced sampling techniques, specifically bias exchange metadynamics. This work represents a first systematic attempt to evaluate the conformations and the corresponding free energy of a large, clinically relevant disordered peptide in solution across force fields. The NMR chemical shifts of rIAPP were calculated for each of the force fields using their respective free energy maps, allowing us to quantitatively assess their predictions. We show that the predicted distribution of secondary structures is sensitive to the choice of force-field: Gromos53a6 is biased towards β-hairpins, while CHARMM22/CMAP predicts structures that are overly α-helical. OPLS-AA/L favors disordered structures. Amberff99sb*-ILDN, AmberFF03w and CHARMM22* provide the balance between secondary structures that is most consistent with available experimental data. In contrast to previous reports, our findings suggest that the equilibrium conformations of human and rat amylin are remarkably similar, but that subtle differences arise in transient alpha-helical and beta-strand containing structures that the human peptide can more readily adopt. We hypothesize that these transient states enable dynamic pathways that facilitate the formation of aggregates and, eventually, amyloid fibrils. PMID:26221949

Secondary structure of rat and human amylin across force fields

DOE PAGES

Hoffmann, Kyle Quynn; McGovern, Michael; Chiu, Chi -cheng; ...

2015-07-29

The aggregation of human amylin has been strongly implicated in the progression of Type II diabetes. This 37-residue peptide forms a variety of secondary structures, including random coils, α-helices, and β-hairpins. The balance between these structures depends on the chemical environment, making amylin an ideal candidate to examine inherent biases in force fields. Rat amylin differs from human amylin by only 6 residues; however, it does not form fibrils. Therefore it provides a useful complement to human amylin in studies of the key events along the aggregation pathway. In this work, the free energy of rat and human amylin wasmore » determined as a function of α-helix and β-hairpin content for the Gromos96 53a6, OPLS-AA/L, CHARMM22/CMAP, CHARMM22*, Amberff99sb*-ILDN, and Amberff03w force fields using advanced sampling techniques, specifically bias exchange metadynamics. This work represents a first systematic attempt to evaluate the conformations and the corresponding free energy of a large, clinically relevant disordered peptide in solution across force fields. The NMR chemical shifts of rIAPP were calculated for each of the force fields using their respective free energy maps, allowing us to quantitatively assess their predictions. We show that the predicted distribution of secondary structures is sensitive to the choice of force-field: Gromos53a6 is biased towards β-hairpins, while CHARMM22/CMAP predicts structures that are overly α-helical. OPLS-AA/L favors disordered structures. Amberff99sb*-ILDN, AmberFF03w and CHARMM22* provide the balance between secondary structures that is most consistent with available experimental data. In contrast to previous reports, our findings suggest that the equilibrium conformations of human and rat amylin are remarkably similar, but that subtle differences arise in transient alpha-helical and beta-strand containing structures that the human peptide can more readily adopt. We hypothesize that these transient states enable dynamic pathways that facilitate the formation of aggregates and, eventually, amyloid fibrils.« less

Action potentials reliably invade axonal arbors of rat neocortical neurons

PubMed Central

Cox, Charles L.; Denk, Winfried; Tank, David W.; Svoboda, Karel

2000-01-01

Neocortical pyramidal neurons have extensive axonal arborizations that make thousands of synapses. Action potentials can invade these arbors and cause calcium influx that is required for neurotransmitter release and excitation of postsynaptic targets. Thus, the regulation of action potential invasion in axonal branches might shape the spread of excitation in cortical neural networks. To measure the reliability and extent of action potential invasion into axonal arbors, we have used two-photon excitation laser scanning microscopy to directly image action-potential-mediated calcium influx in single varicosities of layer 2/3 pyramidal neurons in acute brain slices. Our data show that single action potentials or bursts of action potentials reliably invade axonal arbors over a range of developmental ages (postnatal 10–24 days) and temperatures (24°C-30°C). Hyperpolarizing current steps preceding action potential initiation, protocols that had previously been observed to produce failures of action potential propagation in cultured preparations, were ineffective in modulating the spread of action potentials in acute slices. Our data show that action potentials reliably invade the axonal arbors of neocortical pyramidal neurons. Failures in synaptic transmission must therefore originate downstream of action potential invasion. We also explored the function of modulators that inhibit presynaptic calcium influx. Consistent with previous studies, we find that adenosine reduces action-potential-mediated calcium influx in presynaptic terminals. This reduction was observed in all terminals tested, suggesting that some modulatory systems are expressed homogeneously in most terminals of the same neuron. PMID:10931955

[Patterns of action potential firing in cortical neurons of neonatal mice and their electrophysiological property].

PubMed

Furong, Liu; Shengtian, L I

2016-05-25

To investigate patterns of action potential firing in cortical heurons of neonatal mice and their electrophysiological properties. The passive and active membrane properties of cortical neurons from 3-d neonatal mice were observed by whole-cell patch clamp with different voltage and current mode. Three patterns of action potential firing were identified in response to depolarized current injection. The effects of action potential firing patterns on voltage-dependent inward and outward current were found. Neurons with three different firing patterns had different thresholds of depolarized current. In the morphology analysis of action potential, the three type neurons were different in rise time, duration, amplitude and threshold of the first action potential evoked by 80 pA current injection. The passive properties were similar in three patterns of action potential firing. These results indicate that newborn cortical neurons exhibit different patterns of action potential firing with different action potential parameters such as shape and threshold.

Office immunotherapy in chronic inflammatory demyelinating polyneuropathy and multifocal motor neuropathy.

PubMed

Dyck, Peter J; Taylor, Bruce V; Davies, Jenny L; Mauermann, Michelle L; Litchy, William J; Klein, Christopher J; Dyck, P James B

2015-10-01

Intravenous immunoglobulin [IVIg], plasma exchange [PE], and corticosteroids are efficacious treatment in chronic inflammatory demyelinating polyneuropathy [CIDP]. IVIg is effective in multifocal motor neuropathy [MMN]. NIS, NIS-weakness, sum scores of raw amplitudes of motor fiber (CMAPs) amplitudes, and Dyck/Rankin score provided reliable measures to detect and scale abnormality and reflect change; they are therefore ideal for office management of response-based immunotherapy (R-IRx) of CIDP. Using efficacious R-IRx, a large early and late therapeutic response (≥ one-fourth were in remission or had recovered) was demonstrated in CIDP. In MMN only an early improvement with late non-significant worsening was observed. The difference in immunotherapy response supports a fundamental difference between CIDP (immune attack on Schwann cells and myelin) and MMN (attack on nodes of Ranvier and axons). © 2015 Wiley Periodicals, Inc.

Office Immunotherapy in Chronic Inflammatoryh Demyelinating Polyneuropathy and Multifocal Motor Neuropathy

PubMed Central

Dyck, Peter J.; Taylor, Bruce V.; Davies, Jenny L.; Mauermann, Michelle L.; Litchy, William J.; Klein, Christopher J.; Dyck, P. James B.

2015-01-01

Background Intravenous immunoglobulin [IVIg], plasma exchange [PE], and corticosteroids are efficacious treatment in chronic inflammatory demyelinating polyneuropathy [CIDP]. IVIg is effective in multifocal motor neuropathy [MMN]. Objective and Methods Results and Conclusions NIS, NIS-weakness, sum scores of raw amplitudes of motor fiber (CMAPs) amplitudes, and Dyck/Rankin score provided reliable measures to detect and scale abnormality and reflect change; they are therefore ideal for office management of response-basedimmunotherapy (R-IRx) of CIDP. Using efficacious R-IRx, a large early and late therapeutic response (≥ one-fourth were in remission or had recovered) was demonstrated in CIDP. In MMN only an early improvement with late non-significant worsening was observed. The difference in immunotherapy response supports a fundamental difference between CIDP (immune attack on Schwann cells and myelin) and MMN (attack on nodes of Ranvier and axons). PMID:25976871

Role of action potential configuration and the contribution of Ca2+ and K+ currents to isoprenaline-induced changes in canine ventricular cells

PubMed Central

Szentandrássy, N; Farkas, V; Bárándi, L; Hegyi, B; Ruzsnavszky, F; Horváth, B; Bányász, T; Magyar, J; Márton, I; Nánási, PP

2012-01-01

BACKGROUND AND PURPOSE Although isoprenaline (ISO) is known to activate several ion currents in mammalian myocardium, little is known about the role of action potential morphology in the ISO-induced changes in ion currents. Therefore, the effects of ISO on action potential configuration, L-type Ca2+ current (ICa), slow delayed rectifier K+ current (IKs) and fast delayed rectifier K+ current (IKr) were studied and compared in a frequency-dependent manner using canine isolated ventricular myocytes from various transmural locations. EXPERIMENTAL APPROACH Action potentials were recorded with conventional sharp microelectrodes; ion currents were measured using conventional and action potential voltage clamp techniques. KEY RESULTS In myocytes displaying a spike-and-dome action potential configuration (epicardial and midmyocardial cells), ISO caused reversible shortening of action potentials accompanied by elevation of the plateau. ISO-induced action potential shortening was absent in endocardial cells and in myocytes pretreated with 4-aminopyridine. Application of the IKr blocker E-4031 failed to modify the ISO effect, while action potentials were lengthened by ISO in the presence of the IKs blocker HMR-1556. Both action potential shortening and elevation of the plateau were prevented by pretreatment with the ICa blocker nisoldipine. Action potential voltage clamp experiments revealed a prominent slowly inactivating ICa followed by a rise in IKs, both currents increased with increasing the cycle length. CONCLUSIONS AND IMPLICATIONS The effect of ISO in canine ventricular cells depends critically on action potential configuration, and the ISO-induced activation of IKs– but not IKr– may be responsible for the observed shortening of action potentials. PMID:22563726

Role of action potential configuration and the contribution of C²⁺a and K⁺ currents to isoprenaline-induced changes in canine ventricular cells.

PubMed

Szentandrássy, N; Farkas, V; Bárándi, L; Hegyi, B; Ruzsnavszky, F; Horváth, B; Bányász, T; Magyar, J; Márton, I; Nánási, P P

2012-10-01

Although isoprenaline (ISO) is known to activate several ion currents in mammalian myocardium, little is known about the role of action potential morphology in the ISO-induced changes in ion currents. Therefore, the effects of ISO on action potential configuration, L-type Ca²⁺ current (I(Ca)), slow delayed rectifier K⁺ current (I(Ks)) and fast delayed rectifier K⁺ current (I(Kr)) were studied and compared in a frequency-dependent manner using canine isolated ventricular myocytes from various transmural locations. Action potentials were recorded with conventional sharp microelectrodes; ion currents were measured using conventional and action potential voltage clamp techniques. In myocytes displaying a spike-and-dome action potential configuration (epicardial and midmyocardial cells), ISO caused reversible shortening of action potentials accompanied by elevation of the plateau. ISO-induced action potential shortening was absent in endocardial cells and in myocytes pretreated with 4-aminopyridine. Application of the I(Kr) blocker E-4031 failed to modify the ISO effect, while action potentials were lengthened by ISO in the presence of the I(Ks) blocker HMR-1556. Both action potential shortening and elevation of the plateau were prevented by pretreatment with the I(Ca) blocker nisoldipine. Action potential voltage clamp experiments revealed a prominent slowly inactivating I(Ca) followed by a rise in I(Ks) , both currents increased with increasing the cycle length. The effect of ISO in canine ventricular cells depends critically on action potential configuration, and the ISO-induced activation of I(Ks) - but not I(Kr) - may be responsible for the observed shortening of action potentials. © 2012 The Authors. British Journal of Pharmacology © 2012 The British Pharmacological Society.

Characteristics of action potentials and their underlying outward currents in rat taste receptor cells.

PubMed

Chen, Y; Sun, X D; Herness, S

1996-02-01

1. Taste receptor cells produce action potentials as a result of transduction mechanisms that occur when these cells are stimulated with tastants. These action potentials are thought to be key signaling events in relaying information to the central nervous system. We explored the ionic basis of action potentials from dissociated posterior rat taste cells using the patch-clamp recording technique in both voltage-clamp and current-clamp modes. 2. Action potentials were evoked by intracellular injection of depolarizing current pulses from a holding potential of -80 mV. The threshold potential for firing of action potentials was approximately -35 mV; the input resistance of these cells averaged 6.9 G omega. With long depolarizing pulses, two or three action potentials could be elicited with successive attenuation of the spike height. Afterhyperpolarizations were observed often. 3. Both sodium and calcium currents contribute to depolarizing phases of the action potential. Action potentials were blocked completely in the presence of the sodium channel blocker tetrodotoxin. Calcium contributions could be visualized as prolonged calcium plateaus when repolarizing potassium currents were blocked and barium was used as a charge carrier. 4. Outward currents were composed of sustained delayed rectifier current, transient potassium current, and calcium-activated potassium current. Transient and sustained potassium currents activated close to -30 mV and increased monotonically with further depolarization. Up to half the outward current inactivated with decay constants on the order of seconds. Sustained and transient currents displayed steep voltage dependence in conductance and inactivation curves. Half inactivation occurred at -20 +/- 3.1 mV (mean +/- SE) with a decrease of 11.2 +/- 0.5 mV per e-fold. Half maximal conductance occurred at 3.6 +/- 1.8 mV and increased 12.2 +/- 0.6 mV per e-fold. Calcium-activated potassium current was evidenced by application of apamin and the use of calcium-free bathing solution. It was most obvious at more depolarized holding potentials that inactivated much of the transient and sustained outward currents. 5. Potassium currents contribute to both the repolarization and afterhyperpolarization phases of the action potential. These currents were blocked by bath application of tetraethylammonium, which also substantially broadened the action potential. Application of 4-aminopyridine was able to selectively block transient potassium currents without affecting sustained currents. This also broadened the action potential as well as eliminated the afterhyperpolarization. 6. A second type of action potential was observed that differed in duration. These slow action potentials had t1/2 durations of 9.6 ms compared with 1.4 ms for fast action potentials. Input resistances of the two groups were indistinguishable. Approximately one-fourth of the cells eliciting action potentials were of the slow type. 7. Cells eliciting fast action potentials had large outward currents capable of producing a quick repolarization, whereas cells with slow action potentials had small outward currents by comparison. The average values of fast cells were 2,563 pA and 1.4 ms compared with 373 pA and 9.6 ms for slow cells. Current and duration values were related exponentially. No significant difference was noted for inward currents. 8. These results suggest that many taste receptor cells conduct action potentials, which may be classified broadly into two groups on the basis of action potential duration and potassium current magnitude. These groups may be related to cell turnover. The physiological role of action potentials remains to be elucidated but may be important for communication within the taste bud as well as to the afferent nerve.

State and location dependence of action potential metabolic cost in cortical pyramidal neurons.

PubMed

Hallermann, Stefan; de Kock, Christiaan P J; Stuart, Greg J; Kole, Maarten H P

2012-06-03

Action potential generation and conduction requires large quantities of energy to restore Na(+) and K(+) ion gradients. We investigated the subcellular location and voltage dependence of this metabolic cost in rat neocortical pyramidal neurons. Using Na(+)/K(+) charge overlap as a measure of action potential energy efficiency, we found that action potential initiation in the axon initial segment (AIS) and forward propagation into the axon were energetically inefficient, depending on the resting membrane potential. In contrast, action potential backpropagation into dendrites was efficient. Computer simulations predicted that, although the AIS and nodes of Ranvier had the highest metabolic cost per membrane area, action potential backpropagation into the dendrites and forward propagation into axon collaterals dominated energy consumption in cortical pyramidal neurons. Finally, we found that the high metabolic cost of action potential initiation and propagation down the axon is a trade-off between energy minimization and maximization of the conduction reliability of high-frequency action potentials.

Voltage-gated sodium channel expression and action potential generation in differentiated NG108-15 cells.

PubMed

Liu, Jinxu; Tu, Huiyin; Zhang, Dongze; Zheng, Hong; Li, Yu-Long

2012-10-25

The generation of action potential is required for stimulus-evoked neurotransmitter release in most neurons. Although various voltage-gated ion channels are involved in action potential production, the initiation of the action potential is mainly mediated by voltage-gated Na+ channels. In the present study, differentiation-induced changes of mRNA and protein expression of Na+ channels, Na+ currents, and cell membrane excitability were investigated in NG108-15 cells. Whole-cell patch-clamp results showed that differentiation (9 days) didn't change cell membrane excitability, compared to undifferentiated state. But differentiation (21 days) induced the action potential generation in 45.5% of NG108-15 cells (25/55 cells). In 9-day-differentiated cells, Na+ currents were mildly increased, which was also found in 21-day differentiated cells without action potential. In 21-day differentiated cells with action potential, Na+ currents were significantly enhanced. Western blot data showed that the expression of Na+ channels was increased with differentiated-time dependent manner. Single-cell real-time PCR data demonstrated that the expression of Na+ channel mRNA was increased by 21 days of differentiation in NG108-15 cells. More importantly, the mRNA level of Na+ channels in cells with action potential was higher than that in cells without action potential. Differentiation induces expression of voltage-gated Na+ channels and action potential generation in NG108-15 cells. A high level of the Na+ channel density is required for differentiation-triggered action potential generation.

Effects of premature stimulation on HERG K+ channels

PubMed Central

Lu, Yu; Mahaut-Smith, Martyn P; Varghese, Anthony; Huang, Christopher L-H; Kemp, Paul R; Vandenberg, Jamie I

2001-01-01

The unusual kinetics of human ether-à-go-go-related gene (HERG) K+ channels are consistent with a role in the suppression of arrhythmias initiated by premature beats. Action potential clamp protocols were used to investigate the effect of premature stimulation on HERG K+ channels, transfected in Chinese hamster ovary cells, at 37 °C. HERG K+ channel currents peaked during the terminal repolarization phase of normally paced action potential waveforms. However, the magnitude of the current and the time point at which conductance was maximal depended on the type of action potential waveform used (epicardial, endocardial, Purkinje fibre or atrial). HERG K+ channel currents recorded during premature action potentials consisted of an early transient outward current followed by a sustained outward current. The magnitude of the transient current component showed a biphasic dependence on the coupling interval between the normally paced and premature action potentials and was maximal at a coupling interval equivalent to 90% repolarization (APD90) for ventricular action potentials. The largest transient current response occurred at shorter coupling intervals for Purkinje fibre (APD90– 20 ms) and atrial (APD90– 30 ms) action potentials. The magnitude of the sustained current response following premature stimulation was similar to that recorded during the first action potential for ventricular action potential waveforms. However, for Purkinje and atrial action potentials the sustained current response was significantly larger during the premature action potential than during the normally paced action potential. A Markov model that included three closed states, one open and one inactivated state with transitions permitted between the pre-open closed state and the inactivated state, successfully reproduced our results for the effects of premature stimuli, both during square pulse and action potential clamp waveforms. These properties of HERG K+ channels may help to suppress arrhythmias initiated by early afterdepolarizations and premature beats in the ventricles, Purkinje fibres or atria. PMID:11744759

Electrophysiology of neurones of the inferior mesenteric ganglion of the cat.

PubMed Central

Julé, Y; Szurszewski, J H

1983-01-01

Intracellular recordings were obtained from cells in vitro in the inferior mesenteric ganglia of the cat. Neurones could be classified into three types: non-spontaneous, irregular discharging and regular discharging neurones. Non-spontaneous neurones had a stable resting membrane potential and responded with action potentials to indirect preganglionic nerve stimulation and to intracellular injection of depolarizing current. Irregular discharging neurones were characterized by a discharge of excitatory post-synaptic potentials (e.p.s.p.s.) which sometimes gave rise to action potentials. This activity was abolished by hexamethonium bromide, chlorisondamine and d-tubocurarine chloride. Tetrodotoxin and a low Ca2+ -high Mg2+ solution also blocked on-going activity in irregular discharging neurones. Regular discharging neurones were characterized by a rhythmic discharge of action potentials. Each action potential was preceded by a gradual depolarization of the intracellularly recorded membrane potential. Intracellular injection of hyperpolarizing current abolished the regular discharge of action potential. No synaptic potentials were observed during hyperpolarization of the membrane potential. Nicotinic, muscarinic and adrenergic receptor blocking drugs did not modify the discharge of action potentials in regular discharging neurones. A low Ca2+ -high Mg2+ solution also had no effect on the regular discharge of action potentials. Interpolation of an action potential between spontaneous action potentials in regular discharging neurones reset the rhythm of discharge. It is suggested that regular discharging neurones were endogenously active and that these neurones provided synaptic input to irregular discharging neurones. PMID:6140310

Electrophysiology of neurones of the inferior mesenteric ganglion of the cat.

PubMed

Julé, Y; Szurszewski, J H

1983-11-01

Intracellular recordings were obtained from cells in vitro in the inferior mesenteric ganglia of the cat. Neurones could be classified into three types: non-spontaneous, irregular discharging and regular discharging neurones. Non-spontaneous neurones had a stable resting membrane potential and responded with action potentials to indirect preganglionic nerve stimulation and to intracellular injection of depolarizing current. Irregular discharging neurones were characterized by a discharge of excitatory post-synaptic potentials (e.p.s.p.s.) which sometimes gave rise to action potentials. This activity was abolished by hexamethonium bromide, chlorisondamine and d-tubocurarine chloride. Tetrodotoxin and a low Ca2+ -high Mg2+ solution also blocked on-going activity in irregular discharging neurones. Regular discharging neurones were characterized by a rhythmic discharge of action potentials. Each action potential was preceded by a gradual depolarization of the intracellularly recorded membrane potential. Intracellular injection of hyperpolarizing current abolished the regular discharge of action potential. No synaptic potentials were observed during hyperpolarization of the membrane potential. Nicotinic, muscarinic and adrenergic receptor blocking drugs did not modify the discharge of action potentials in regular discharging neurones. A low Ca2+ -high Mg2+ solution also had no effect on the regular discharge of action potentials. Interpolation of an action potential between spontaneous action potentials in regular discharging neurones reset the rhythm of discharge. It is suggested that regular discharging neurones were endogenously active and that these neurones provided synaptic input to irregular discharging neurones.

Dynamics of action potential initiation in the GABAergic thalamic reticular nucleus in vivo.

PubMed

Muñoz, Fabián; Fuentealba, Pablo

2012-01-01

Understanding the neural mechanisms of action potential generation is critical to establish the way neural circuits generate and coordinate activity. Accordingly, we investigated the dynamics of action potential initiation in the GABAergic thalamic reticular nucleus (TRN) using in vivo intracellular recordings in cats in order to preserve anatomically-intact axo-dendritic distributions and naturally-occurring spatiotemporal patterns of synaptic activity in this structure that regulates the thalamic relay to neocortex. We found a wide operational range of voltage thresholds for action potentials, mostly due to intrinsic voltage-gated conductances and not synaptic activity driven by network oscillations. Varying levels of synchronous synaptic inputs produced fast rates of membrane potential depolarization preceding the action potential onset that were associated with lower thresholds and increased excitability, consistent with TRN neurons performing as coincidence detectors. On the other hand the presence of action potentials preceding any given spike was associated with more depolarized thresholds. The phase-plane trajectory of the action potential showed somato-dendritic propagation, but no obvious axon initial segment component, prominent in other neuronal classes and allegedly responsible for the high onset speed. Overall, our results suggest that TRN neurons could flexibly integrate synaptic inputs to discharge action potentials over wide voltage ranges, and perform as coincidence detectors and temporal integrators, supported by a dynamic action potential threshold.

Mechanisms and consequences of action potential burst firing in rat neocortical pyramidal neurons

PubMed Central

Williams, Stephen R; Stuart, Greg J

1999-01-01

Electrophysiological recordings and pharmacological manipulations were used to investigate the mechanisms underlying the generation of action potential burst firing and its postsynaptic consequences in visually identified rat layer 5 pyramidal neurons in vitro.Based upon repetitive firing properties and subthreshold membrane characteristics, layer 5 pyramidal neurons were separated into three classes: regular firing and weak and strong intrinsically burst firing.High frequency (330 ± 10 Hz) action potential burst firing was abolished or greatly weakened by the removal of Ca2+ (n = 5) from, or by the addition of the Ca2+ channel antagonist Ni2+ (250–500 μm; n = 8) to, the perfusion medium.The blockade of apical dendritic sodium channels by the local dendritic application of TTX (100 nm; n = 5) abolished or greatly weakened action potential burst firing, as did the local apical dendritic application of Ni2+ (1 mm; n = 5).Apical dendritic depolarisation resulted in low frequency (157 ± 26 Hz; n = 6) action potential burst firing in regular firing neurons, as classified by somatic current injection. The intensity of action potential burst discharges in intrinsically burst firing neurons was facilitated by dendritic depolarisation (n = 11).Action potential amplitude decreased throughout a burst when recorded somatically, suggesting that later action potentials may fail to propagate axonally. Axonal recordings demonstrated that each action potential in a burst is axonally initiated and that no decrement in action potential amplitude is apparent in the axon > 30 μm from the soma.Paired recordings (n = 16) from synaptically coupled neurons indicated that each action potential in a burst could cause transmitter release. EPSPs or EPSCs evoked by a presynaptic burst of action potentials showed use-dependent synaptic depression.A postsynaptic, TTX-sensitive voltage-dependent amplification process ensured that later EPSPs in a burst were amplified when generated from membrane potentials positive to -60 mV, providing a postsynaptic mechanism that counteracts use-dependent depression at synapses between layer 5 pyramidal neurons. PMID:10581316

The human ether-a-go-go-related gene (hERG) current inhibition selectively prolongs action potential of midmyocardial cells to augment transmural dispersion.

PubMed

Yasuda, C; Yasuda, S; Yamashita, H; Okada, J; Hisada, T; Sugiura, S

2015-08-01

The majority of drug induced arrhythmias are related to the prolongation of action potential duration following inhibition of rapidly activating delayed rectifier potassium current (I(Kr)) mediated by the hERG channel. However, for arrhythmias to develop and be sustained, not only the prolongation of action potential duration but also its transmural dispersion are required. Herein, we evaluated the effect of hERG inhibition on transmural dispersion of action potential duration using the action potential clamp technique that combined an in silico myocyte model with the actual I(Kr) measurement. Whole cell I(Kr) current was measured in Chinese hamster ovary cells stably expressing the hERG channel. The measured current was coupled with models of ventricular endocardial, M-, and epicardial cells to calculate the action potentials. Action potentials were evaluated under control condition and in the presence of 1, 10, or 100 μM disopyramide, an hERG inhibitor. Disopyramide dose-dependently increased the action potential durations of the three cell types. However, action potential duration of M-cells increased disproportionately at higher doses, and was significantly different from that of epicardial and endocardial cells (dispersion of repolarization). By contrast, the effects of disopyramide on peak I(Kr) and instantaneous current-voltage relation were similar in all cell types. Simulation study suggested that the reduced repolarization reserve of M-cell with smaller amount of slowly activating delayed rectifier potassium current levels off at longer action potential duration to make such differences. The action potential clamp technique is useful for studying the mechanism of arrhythmogenesis by hERG inhibition through the transmural dispersion of repolarization.

Dynamics of Action Potential Initiation in the GABAergic Thalamic Reticular Nucleus In Vivo

PubMed Central

Muñoz, Fabián; Fuentealba, Pablo

2012-01-01

Understanding the neural mechanisms of action potential generation is critical to establish the way neural circuits generate and coordinate activity. Accordingly, we investigated the dynamics of action potential initiation in the GABAergic thalamic reticular nucleus (TRN) using in vivo intracellular recordings in cats in order to preserve anatomically-intact axo-dendritic distributions and naturally-occurring spatiotemporal patterns of synaptic activity in this structure that regulates the thalamic relay to neocortex. We found a wide operational range of voltage thresholds for action potentials, mostly due to intrinsic voltage-gated conductances and not synaptic activity driven by network oscillations. Varying levels of synchronous synaptic inputs produced fast rates of membrane potential depolarization preceding the action potential onset that were associated with lower thresholds and increased excitability, consistent with TRN neurons performing as coincidence detectors. On the other hand the presence of action potentials preceding any given spike was associated with more depolarized thresholds. The phase-plane trajectory of the action potential showed somato-dendritic propagation, but no obvious axon initial segment component, prominent in other neuronal classes and allegedly responsible for the high onset speed. Overall, our results suggest that TRN neurons could flexibly integrate synaptic inputs to discharge action potentials over wide voltage ranges, and perform as coincidence detectors and temporal integrators, supported by a dynamic action potential threshold. PMID:22279567

Decision making and action implementation: evidence for an early visually triggered motor activation specific to potential actions.

PubMed

Tandonnet, Christophe; Garry, Michael I; Summers, Jeffery J

2013-07-01

To make a decision may rely on accumulating evidence in favor of one alternative until a threshold is reached. Sequential-sampling models differ by the way of accumulating evidence and the link with action implementation. Here, we tested a model's prediction of an early action implementation specific to potential actions. We assessed the dynamics of action implementation in go/no-go and between-hand choice tasks by transcranial magnetic stimulation of the motor cortex (single- or paired-pulse TMS; 3-ms interstimulus interval). Prior to implementation of the selected action, the amplitude of the motor evoked potential first increased whatever the visual stimulus but only for the hand potentially involved in the to-be-produced action. These findings suggest that visual stimuli can trigger an early motor activation specific to potential actions, consistent with race-like models with continuous transmission between decision making and action implementation. Copyright © 2013 Society for Psychophysiological Research.

The effects of saxitoxin and tetrodotoxin on nerve conduction in the presence of lithium ions and of magnesium ions

PubMed Central

Evans, M. H.

1969-01-01

1. It has been shown that nerve fibres from rat cauda equina will conduct action potentials after immersion in saline in which lithium chloride is substituted for sodium chloride. 2. Both saxitoxin and tetrodotoxin inhibit lithium-generated action potentials. The concentration of toxin needed to inhibit the lithium-generated action potentials is similar to that needed to inhibit sodium-generated action potentials. 3. If magnesium chloride is added to the saline to give a concentration of 10-15 mM there is usually a slight fall in amplitude of the compound action potential. Saxitoxin and tetrodotoxin now inhibit the action potential to a greater degree than in the absence of magnesium ions. PMID:5789802

Actions and mechanisms of action of novel analogues of sotalol on guinea-pig and rabbit ventricular cells.

PubMed Central

Connors, S. P.; Gill, E. W.; Terrar, D. A.

1992-01-01

1. The actions and mechanisms of action of novel analogues of sotalol which prolong cardiac action potentials were investigated in guinea-pig and rabbit isolated ventricular cells. 2. In guinea-pig and rabbit cells the compounds significantly prolonged action potential duration at 20% and 90% repolarization levels without affecting resting membrane potential. In guinea-pig but not rabbit cells there was an increase in action potential amplitude and in rabbit cells there was no change in the shape or position of the 'notch' in the action potential. 3. Possible mechanisms of action were studied in more detail in the case of compound II (1-(4-methanesulphonamidophenoxy)-3-(N-methyl 3,4 dichlorophenylethylamino)-2-propanol). Prolongation of action potential duration continued to occur in the presence of nisoldipine, and calcium currents recorded under voltage-clamp conditions were not reduced by compound II (1 microM). Action potential prolongation by compound II was also unaffected in the presence of 10 microM tetrodotoxin. 4. Compound II (1 microM) did not influence IK1 assessed from the current during ramp changes in membrane potential (20 mV s-1) over the range -90 to -10 mV. 5. Compound II (1 microM) blocked time-dependent delayed rectifier potassium current (IK) activated by step depolarizations and recorded as an outward tail following repolarization. When a submaximal concentration (50 nM) was applied there was no change in the apparent reversal potential of IK.(ABSTRACT TRUNCATED AT 250 WORDS) PMID:1393293

Alteration of neural action potential patterns by axonal stimulation: the importance of stimulus location.

PubMed

Crago, Patrick E; Makowski, Nathaniel S

2014-10-01

Stimulation of peripheral nerves is often superimposed on ongoing motor and sensory activity in the same axons, without a quantitative model of the net action potential train at the axon endpoint. We develop a model of action potential patterns elicited by superimposing constant frequency axonal stimulation on the action potentials arriving from a physiologically activated neural source. The model includes interactions due to collision block, resetting of the neural impulse generator, and the refractory period of the axon at the point of stimulation. Both the mean endpoint firing rate and the probability distribution of the action potential firing periods depend strongly on the relative firing rates of the two sources and the intersite conduction time between them. When the stimulus rate exceeds the neural rate, neural action potentials do not reach the endpoint and the rate of endpoint action potentials is the same as the stimulus rate, regardless of the intersite conduction time. However, when the stimulus rate is less than the neural rate, and the intersite conduction time is short, the two rates partially sum. Increases in stimulus rate produce non-monotonic increases in endpoint rate and continuously increasing block of neurally generated action potentials. Rate summation is reduced and more neural action potentials are blocked as the intersite conduction time increases. At long intersite conduction times, the endpoint rate simplifies to being the maximum of either the neural or the stimulus rate. This study highlights the potential of increasing the endpoint action potential rate and preserving neural information transmission by low rate stimulation with short intersite conduction times. Intersite conduction times can be decreased with proximal stimulation sites for muscles and distal stimulation sites for sensory endings. The model provides a basis for optimizing experiments and designing neuroprosthetic interventions involving motor or sensory stimulation.

The role of Na-Ca exchange current in the cardiac action potential.

PubMed

Janvier, N C; Boyett, M R

1996-07-01

Since 1981, when Mullins published his provocative book proposing that the Na-Ca exchanger is electrogenic, it has been shown, first by computer simulation by Noble and later by experiment by various investigators, that inward iNaCa triggered by the Ca2+ transient is responsible for the low plateau of the atrial action potential and contributes to the high plateau of the ventricular action potential. Reduction or complete block of inward iNaCa by buffering intracellular Ca2+ with EGTA or BAPTA, by blocking SR Ca2+ release or by substituting extracellular Na+ with Li+ can result in a shortening of the action potential. The effect of block of outward iNaCa or complete block of both inward and outward iNaCa on the action potential has not been investigated experimentally, because of the lack of a suitable blocker, and remains a goal for the future. An increase in the intracellular Na+ concentration (after the application of cardiac glycoside or an increase in heart rate) or an increase in extracellular Ca2+ are believed to lead to an outward shift in iNaCa at plateau potentials and a shortening of the action potential. Changes in the Ca2+ transient are expected to result in changes in inward iNaCa and thus the action potential. This may explain the shortening of the premature action potential as well as the prolongation of the action potential when a muscle is allowed to shorten during the action potential. Inward iNaCa may play an important role in both normal and abnormal pacemaker activity in the heart.

Simulation of action potential propagation in plants.

PubMed

Sukhov, Vladimir; Nerush, Vladimir; Orlova, Lyubov; Vodeneev, Vladimir

2011-12-21

Action potential is considered to be one of the primary responses of a plant to action of various environmental factors. Understanding plant action potential propagation mechanisms requires experimental investigation and simulation; however, a detailed mathematical model of plant electrical signal transmission is absent. Here, the mathematical model of action potential propagation in plants has been worked out. The model is a two-dimensional system of excitable cells; each of them is electrically coupled with four neighboring ones. Ion diffusion between excitable cell apoplast areas is also taken into account. The action potential generation in a single cell has been described on the basis of our previous model. The model simulates active and passive signal transmission well enough. It has been used to analyze theoretically the influence of cell to cell electrical conductivity and H(+)-ATPase activity on the signal transmission in plants. An increase in cell to cell electrical conductivity has been shown to stimulate an increase in the length constant, the action potential propagation velocity and the temperature threshold, while the membrane potential threshold being weakly changed. The growth of H(+)-ATPase activity has been found to induce the increase of temperature and membrane potential thresholds and the reduction of the length constant and the action potential propagation velocity. Copyright © 2011 Elsevier Ltd. All rights reserved.

[Loudness optimized registration of compound action potential in cochlear implant recipients].

PubMed

Berger, Klaus; Hocke, Thomas; Hessel, Horst

2017-11-01

Background Postoperative measurements of compound action potentials are not always possible due to the insufficient acceptance of the CI-recipients. This study investigated the impact of different parameters on the acceptance of the measurements. Methods Compound action potentials of 16 CI recipients were measured with different pulse-widths. Recipients performed a loudness rating at the potential thresholds with the different sequences. Results Compound action potentials obtained with higher pulse-widths were rated softer than those obtained with smaller pulse-widths. Conclusions Compound action potentials measured with higher pulse-widths generate a gap between loudest acceptable presentation level and potential threshold. This gap contributes to a higher acceptance of postoperative measurements. Georg Thieme Verlag KG Stuttgart · New York.

Inducing repetitive action potential firing in neurons via synthesized photoresponsive nanoscale cellular prostheses.

PubMed

Lu, Siyuan; Madhukar, Anupam

2013-02-01

Recently we reported an analysis that examined the potential of synthesized photovoltaic functional abiotic nanosystems (PVFANs) to modulate membrane potential and activate action potential firing in neurons. Here we extend the analysis to delineate the requirements on the electronic energy levels and the attendant photophysical properties of the PVFANs to induce repetitive action potential under continuous light, a capability essential for the proposed potential application of PVFANs as retinal cellular prostheses to compensate for loss of photoreceptors. We find that repetitive action potential firing demands two basic characteristics in the electronic response of the PVFANs: an exponential dependence of the PVFAN excited state decay rate on the membrane potential and a three-state system such that, following photon absorption, the electron decay from the excited state to the ground state is via intermediate state(s) whose lifetime is comparable to the refractory time following an action potential. In this study, the potential of synthetic photovoltaic functional abiotic nanosystems (PVFANs) is examined under continuous light to modulate membrane potential and activate action potential firing in neurons with the proposed potential application of PVFANs as retinal cellular prostheses. Copyright © 2013 Elsevier Inc. All rights reserved.

Effects of K(+) channel openers on spontaneous action potentials in detrusor smooth muscle of the guinea-pig urinary bladder.

PubMed

Takagi, Hiroaki; Hashitani, Hikaru

2016-10-15

The modulation of spontaneous excitability in detrusor smooth muscle (DSM) upon the pharmacological activation of different populations of K(+) channels was investigated. Effects of distinct K(+) channel openers on spontaneous action potentials in DSM of the guinea-pig bladder were examined using intracellular microelectrode techniques. NS1619 (10μM), a large conductance Ca(2+)-activated K(+) (BK) channel opener, transiently increased action potential frequency and then prevented their generation without hyperpolarizing the membrane in a manner sensitive to iberiotoxin (IbTX, 100nM). A higher concentration of NS1619 (30μM) hyperpolarized the membrane and abolished action potential firing. NS309 (10μM) and SKA31 (100μM), small conductance Ca(2+)-activated K(+) (SK) channel openers, dramatically increased the duration of the after-hyperpolarization and then abolished action potential firing in an apamin (100nM)-sensitive manner. Flupirtine (10μM), a Kv7 channel opener, inhibited action potential firing without hyperpolarizing the membrane in a manner sensitive to XE991 (10μM), a Kv7 channel blocker. BRL37344 (10μM), a β3-adrenceptor agonist, or rolipram (10nM), a phosphodiesterase 4 inhibitor, also inhibited action potential firing. A higher concentration of rolipram (100nM) hyperpolarized the DSM and abolished the action potentials. IbTX (100nM) prevented the rolipram-induced blockade of action potentials but not the hyperpolarization. BK and Kv7 channels appear to predominantly contribute to the stabilization of DSM excitability. Spare SK channels could be pharmacologically activated to suppress DSM excitability. BK channels appear to be involved in the cyclic AMP-induced inhibition of action potentials but not the membrane hyperpolarization. Copyright © 2016 Elsevier B.V. All rights reserved.

Imaging Action Potential in Single Mammalian Neurons by Tracking the Accompanying Sub-Nanometer Mechanical Motion.

PubMed

Yang, Yunze; Liu, Xian-Wei; Wang, Hui; Yu, Hui; Guan, Yan; Wang, Shaopeng; Tao, Nongjian

2018-03-28

Action potentials in neurons have been studied traditionally by intracellular electrophysiological recordings and more recently by the fluorescence detection methods. Here we describe a label-free optical imaging method that can measure mechanical motion in single cells with a sub-nanometer detection limit. Using the method, we have observed sub-nanometer mechanical motion accompanying the action potential in single mammalian neurons by averaging the repeated action potential spikes. The shape and width of the transient displacement are similar to those of the electrically recorded action potential, but the amplitude varies from neuron to neuron, and from one region of a neuron to another, ranging from 0.2-0.4 nm. The work indicates that action potentials may be studied noninvasively in single mammalian neurons by label-free imaging of the accompanying sub-nanometer mechanical motion.

Pathological prolongation of action potential duration as a cause of the reduced alpha-adrenoceptor-mediated negative inotropy in streptozotocin-induced diabetic mice myocardium.

PubMed

Kanae, Haruna; Hamaguchi, Shogo; Wakasugi, Yumi; Kusakabe, Taichi; Kato, Keisuke; Namekata, Iyuki; Tanaka, Hikaru

2017-11-01

Effect of pathological prolongation of action potential duration on the α-adrenoceptor-mediated negative inotropy was studied in streptozotocin-induced diabetic mice myocardium. In streptozotocin-treated mouse ventricular myocardium, which had longer duration of action potential than that in control mice, the negative inotropic response induced by phenylephrine was smaller than that in control mice. 4-Aminopyridine prolonged the action potential duration and decreased the negative inotropy in control mice. Cromakalim shortened the action potential duration and increased the negative inotropy in streptozotocin-treated mice. These results suggest that the reduced α-adrenoceptor-mediated inotropy in the diabetic mouse myocardium is partly due to its prolonged action potential. Copyright © 2017 The Authors. Production and hosting by Elsevier B.V. All rights reserved.

Determination of cable parameters in skeletal muscle fibres during repetitive firing of action potentials.

PubMed

Riisager, Anders; Duehmke, Rudy; Nielsen, Ole Bækgaard; Huang, Christopher L; Pedersen, Thomas Holm

2014-10-15

Recent studies in rat muscle fibres show that repetitive firing of action potentials causes changes in fibre resting membrane conductance (Gm) that reflect regulation of ClC-1 Cl(-) and KATP K(+) ion channels. Methodologically, these findings were obtained by inserting two microelectrodes at close proximity in the same fibres enabling measurements of fibre input resistance (Rin) in between action potential trains. Since the fibre length constant (λ) could not be determined, however, the calculation of Gm relied on the assumptions that the specific cytosolic resistivity (Ri) and muscle fibre volume remained constant during the repeated action potential firing. Here we present a three-microelectrode technique that enables determinations of multiple cable parameters in action potential-firing fibres including Rin and λ as well as waveform and conduction velocities of fully propagating action potentials. It is shown that in both rat and mouse extensor digitorum longus (EDL) fibres, action potential firing leads to substantial changes in both muscle fibre volume and Ri. The analysis also showed, however, that regardless of these changes, rat and mouse EDL fibres both exhibited initial decreases in Gm that were eventually followed by a ∼3-fold, fully reversible increase in Gm after the firing of 1450-1800 action potentials. Using this three-electrode method we further show that the latter rise in Gm was closely associated with excitation failures and loss of action potential signal above -20 mV. © 2014 The Authors. The Journal of Physiology © 2014 The Physiological Society.

Determination of cable parameters in skeletal muscle fibres during repetitive firing of action potentials

PubMed Central

Riisager, Anders; Duehmke, Rudy; Nielsen, Ole Bækgaard; Huang, Christopher L; Pedersen, Thomas Holm

2014-01-01

Recent studies in rat muscle fibres show that repetitive firing of action potentials causes changes in fibre resting membrane conductance (Gm) that reflect regulation of ClC-1 Cl− and KATP K+ ion channels. Methodologically, these findings were obtained by inserting two microelectrodes at close proximity in the same fibres enabling measurements of fibre input resistance (Rin) in between action potential trains. Since the fibre length constant (λ) could not be determined, however, the calculation of Gm relied on the assumptions that the specific cytosolic resistivity (Ri) and muscle fibre volume remained constant during the repeated action potential firing. Here we present a three-microelectrode technique that enables determinations of multiple cable parameters in action potential-firing fibres including Rin and λ as well as waveform and conduction velocities of fully propagating action potentials. It is shown that in both rat and mouse extensor digitorum longus (EDL) fibres, action potential firing leads to substantial changes in both muscle fibre volume and Ri. The analysis also showed, however, that regardless of these changes, rat and mouse EDL fibres both exhibited initial decreases in Gm that were eventually followed by a ∼3-fold, fully reversible increase in Gm after the firing of 1450–1800 action potentials. Using this three-electrode method we further show that the latter rise in Gm was closely associated with excitation failures and loss of action potential signal above −20 mV. PMID:25128573

Synaptic depolarization is more effective than back-propagating action potentials during induction of associative long-term potentiation in hippocampal pyramidal neurons.

PubMed

Hardie, Jason; Spruston, Nelson

2009-03-11

Long-term potentiation (LTP) requires postsynaptic depolarization that can result from EPSPs paired with action potentials or larger EPSPs that trigger dendritic spikes. We explored the relative contribution of these sources of depolarization to LTP induction during synaptically driven action potential firing in hippocampal CA1 pyramidal neurons. Pairing of a weak test input with a strong input resulted in large LTP (approximately 75% increase) when the weak and strong inputs were both located in the apical dendrites. This form of LTP did not require somatic action potentials. When the strong input was located in the basal dendrites, the resulting LTP was smaller (< or =25% increase). Pairing the test input with somatically evoked action potentials mimicked this form of LTP. Thus, back-propagating action potentials may contribute to modest LTP, but local synaptic depolarization and/or dendritic spikes mediate a stronger form of LTP that requires spatial proximity of the associated synaptic inputs.

Cardiac action potential imaging

NASA Astrophysics Data System (ADS)

Tian, Qinghai; Lipp, Peter; Kaestner, Lars

2013-06-01

Action potentials in cardiac myocytes have durations in the order of magnitude of 100 milliseconds. In biomedical investigations the documentation of the occurrence of action potentials is often not sufficient, but a recording of the shape of an action potential allows a functional estimation of several molecular players. Therefore a temporal resolution of around 500 images per second is compulsory. In the past such measurements have been performed with photometric approaches limiting the measurement to one cell at a time. In contrast, imaging allows reading out several cells at a time with additional spatial information. Recent developments in camera technologies allow the acquisition with the required speed and sensitivity. We performed action potential imaging on isolated adult cardiomyocytes of guinea pigs utilizing the fluorescent membrane potential sensor di-8-ANEPPS and latest electron-multiplication CCD as well as scientific CMOS cameras of several manufacturers. Furthermore, we characterized the signal to noise ratio of action potential signals of varying sets of cameras, dye concentrations and objective lenses. We ensured that di-8-ANEPPS itself did not alter action potentials by avoiding concentrations above 5 μM. Based on these results we can conclude that imaging is a reliable method to read out action potentials. Compared to conventional current-clamp experiments, this optical approach allows a much higher throughput and due to its contact free concept leaving the cell to a much higher degree undisturbed. Action potential imaging based on isolated adult cardiomyocytes can be utilized in pharmacological cardiac safety screens bearing numerous advantages over approaches based on heterologous expression of hERG channels in cell lines.

A simple model for the generation of the vestibular evoked myogenic potential (VEMP).

PubMed

Wit, Hero P; Kingma, Charlotte M

2006-06-01

To describe the mechanism by which the vestibular evoked myogenic potential is generated. Vestibular evoked myogenic potential generation is modeled by adding a large number of muscle motor unit action potentials. These action potentials occur randomly in time along a 100 ms long time axis. But because between approximately 15 and 20 ms after a loud short sound stimulus (almost) no action potentials are generated during VEMP measurements in human subjects, no action potentials are present in the model during this time. The evoked potential is the result of the lack of amplitude cancellation in the averaged surface electromyogram at the edges of this 5 ms long time interval. The relatively simple model describes generation and some properties of the vestibular evoked myogenic potential very well. It is shown that, in contrast with other evoked potentials (BAEPs, VERs), the vestibular evoked myogenic potential is the result of an interruption of activity and not that of summed synchronized neural action potentials.

A rabbit ventricular action potential model replicating cardiac dynamics at rapid heart rates.

PubMed

Mahajan, Aman; Shiferaw, Yohannes; Sato, Daisuke; Baher, Ali; Olcese, Riccardo; Xie, Lai-Hua; Yang, Ming-Jim; Chen, Peng-Sheng; Restrepo, Juan G; Karma, Alain; Garfinkel, Alan; Qu, Zhilin; Weiss, James N

2008-01-15

Mathematical modeling of the cardiac action potential has proven to be a powerful tool for illuminating various aspects of cardiac function, including cardiac arrhythmias. However, no currently available detailed action potential model accurately reproduces the dynamics of the cardiac action potential and intracellular calcium (Ca(i)) cycling at rapid heart rates relevant to ventricular tachycardia and fibrillation. The aim of this study was to develop such a model. Using an existing rabbit ventricular action potential model, we modified the L-type calcium (Ca) current (I(Ca,L)) and Ca(i) cycling formulations based on new experimental patch-clamp data obtained in isolated rabbit ventricular myocytes, using the perforated patch configuration at 35-37 degrees C. Incorporating a minimal seven-state Markovian model of I(Ca,L) that reproduced Ca- and voltage-dependent kinetics in combination with our previously published dynamic Ca(i) cycling model, the new model replicates experimentally observed action potential duration and Ca(i) transient alternans at rapid heart rates, and accurately reproduces experimental action potential duration restitution curves obtained by either dynamic or S1S2 pacing.

Typical gray matter axons in mammalian brain fail to conduct action potentials faithfully at fever-like temperatures.

PubMed

Pekala, Dobromila; Szkudlarek, Hanna; Raastad, Morten

2016-10-01

We studied the ability of typical unmyelinated cortical axons to conduct action potentials at fever-like temperatures because fever often gives CNS symptoms. We investigated such axons in cerebellar and hippocampal slices from 10 to 25 days old rats at temperatures between 30 and 43°C. By recording with two electrodes along axonal pathways, we confirmed that the axons were able to initiate action potentials, but at temperatures >39°C, the propagation of the action potentials to a more distal recording site was reduced. This temperature-sensitive conduction may be specific for the very thin unmyelinated axons because similar recordings from myelinated CNS axons did not show conduction failures. We found that the conduction fidelity improved with 1 mmol/L TEA in the bath, probably due to block of voltage-sensitive potassium channels responsible for the fast repolarization of action potentials. Furthermore, by recording electrically activated antidromic action potentials from the soma of cerebellar granule cells, we showed that the axons failed less if they were triggered 10-30 msec after another action potential. This was because individual action potentials were followed by a depolarizing after-potential, of constant amplitude and shape, which facilitated conduction of the following action potentials. The temperature-sensitive conduction failures above, but not below, normal body temperature, and the failure-reducing effect of the spike's depolarizing after-potential, are two intrinsic mechanisms in normal gray matter axons that may help us understand how the hyperthermic brain functions. © 2016 The Authors. Physiological Reports published by Wiley Periodicals, Inc. on behalf of the American Physiological Society and The Physiological Society.

Alteration of neural action potential patterns by axonal stimulation: the importance of stimulus location

PubMed Central

Crago, Patrick E; Makowski, Nathan S

2014-01-01

Objective Stimulation of peripheral nerves is often superimposed on ongoing motor and sensory activity in the same axons, without a quantitative model of the net action potential train at the axon endpoint. Approach We develop a model of action potential patterns elicited by superimposing constant frequency axonal stimulation on the action potentials arriving from a physiologically activated neural source. The model includes interactions due to collision block, resetting of the neural impulse generator, and the refractory period of the axon at the point of stimulation. Main Results Both the mean endpoint firing rate and the probability distribution of the action potential firing periods depend strongly on the relative firing rates of the two sources and the intersite conduction time between them. When the stimulus rate exceeds the neural rate, neural action potentials do not reach the endpoint and the rate of endpoint action potentials is the same as the stimulus rate, regardless of the intersite conduction time. However, when the stimulus rate is less than the neural rate, and the intersite conduction time is short, the two rates partially sum. Increases in stimulus rate produce non-monotonic increases in endpoint rate and continuously increasing block of neurally generated action potentials. Rate summation is reduced and more neural action potentials are blocked as the intersite conduction time increases.. At long intersite conduction times, the endpoint rate simplifies to being the maximum of either the neural or the stimulus rate. Significance This study highlights the potential of increasing the endpoint action potential rate and preserving neural information transmission by low rate stimulation with short intersite conduction times. Intersite conduction times can be decreased with proximal stimulation sites for muscles and distal stimulation sites for sensory endings. The model provides a basis for optimizing experiments and designing neuroprosthetic interventions involving motor or sensory stimulation. PMID:25161163

Alteration of neural action potential patterns by axonal stimulation: the importance of stimulus location

NASA Astrophysics Data System (ADS)

Crago, Patrick E.; Makowski, Nathaniel S.

2014-10-01

Objective. Stimulation of peripheral nerves is often superimposed on ongoing motor and sensory activity in the same axons, without a quantitative model of the net action potential train at the axon endpoint. Approach. We develop a model of action potential patterns elicited by superimposing constant frequency axonal stimulation on the action potentials arriving from a physiologically activated neural source. The model includes interactions due to collision block, resetting of the neural impulse generator, and the refractory period of the axon at the point of stimulation. Main results. Both the mean endpoint firing rate and the probability distribution of the action potential firing periods depend strongly on the relative firing rates of the two sources and the intersite conduction time between them. When the stimulus rate exceeds the neural rate, neural action potentials do not reach the endpoint and the rate of endpoint action potentials is the same as the stimulus rate, regardless of the intersite conduction time. However, when the stimulus rate is less than the neural rate, and the intersite conduction time is short, the two rates partially sum. Increases in stimulus rate produce non-monotonic increases in endpoint rate and continuously increasing block of neurally generated action potentials. Rate summation is reduced and more neural action potentials are blocked as the intersite conduction time increases. At long intersite conduction times, the endpoint rate simplifies to being the maximum of either the neural or the stimulus rate. Significance. This study highlights the potential of increasing the endpoint action potential rate and preserving neural information transmission by low rate stimulation with short intersite conduction times. Intersite conduction times can be decreased with proximal stimulation sites for muscles and distal stimulation sites for sensory endings. The model provides a basis for optimizing experiments and designing neuroprosthetic interventions involving motor or sensory stimulation.

Effect of an educational game on university students' learning about action potentials.

PubMed

Luchi, Kelly Cristina Gaviao; Montrezor, Luís Henrique; Marcondes, Fernanda K

2017-06-01

The aim of this study was to evaluate the effect of an educational game that is used for teaching the mechanisms of the action potentials in cell membranes. The game was composed of pieces representing the intracellular and extracellular environments, ions, ion channels, and the Na + -K + -ATPase pump. During the game activity, the students arranged the pieces to demonstrate how the ions move through the membrane in a resting state and during an action potential, linking the ion movement with a graph of the action potential. To test the effect of the game activity on student understanding, first-year dental students were given the game to play at different times in a series of classes teaching resting membrane potential and action potentials. In all experiments, students who played the game performed better in assessments. According to 98% of the students, the game supported the learning process. The data confirm the students' perception, indicating that the educational game improved their understanding about action potentials. Copyright © 2017 the American Physiological Society.

Understanding the electrical behavior of the action potential in terms of elementary electrical sources.

PubMed

Rodriguez-Falces, Javier

2015-03-01

A concept of major importance in human electrophysiology studies is the process by which activation of an excitable cell results in a rapid rise and fall of the electrical membrane potential, the so-called action potential. Hodgkin and Huxley proposed a model to explain the ionic mechanisms underlying the formation of action potentials. However, this model is unsuitably complex for teaching purposes. In addition, the Hodgkin and Huxley approach describes the shape of the action potential only in terms of ionic currents, i.e., it is unable to explain the electrical significance of the action potential or describe the electrical field arising from this source using basic concepts of electromagnetic theory. The goal of the present report was to propose a new model to describe the electrical behaviour of the action potential in terms of elementary electrical sources (in particular, dipoles). The efficacy of this model was tested through a closed-book written exam. The proposed model increased the ability of students to appreciate the distributed character of the action potential and also to recognize that this source spreads out along the fiber as function of space. In addition, the new approach allowed students to realize that the amplitude and sign of the extracellular electrical potential arising from the action potential are determined by the spatial derivative of this intracellular source. The proposed model, which incorporates intuitive graphical representations, has improved students' understanding of the electrical potentials generated by bioelectrical sources and has heightened their interest in bioelectricity. Copyright © 2015 The American Physiological Society.

Selective activation of heteromeric SK channels contributes to action potential repolarization in mouse atrial myocytes.

PubMed

Hancock, Jane M; Weatherall, Kate L; Choisy, Stéphanie C; James, Andrew F; Hancox, Jules C; Marrion, Neil V

2015-05-01

Activation of small conductance calcium-activated potassium (SK) channels is proposed to contribute to repolarization of the action potential in atrial myocytes. This role is controversial, as these cardiac SK channels appear to exhibit an uncharacteristic pharmacology. The objectives of this study were to resolve whether activation of SK channels contributes to atrial action potential repolarization and to determine the likely subunit composition of the channel. The effect of 2 SK channel inhibitors was assessed on outward current evoked in voltage clamp and on action potential duration in perforated patch and whole-cell current clamp recording from acutely isolated mouse atrial myocytes. The presence of SK channel subunits was assessed using immunocytochemistry. A significant component of outward current was reduced by the SK channel blockers apamin and UCL1684. Block by apamin displayed a sensitivity indicating that this current was carried by homomeric SK2 channels. Action potential duration was significantly prolonged by UCL1684, but not by apamin. This effect was accompanied by an increase in beat-to-beat variability and action potential triangulation. This pharmacology was matched by that of expressed heteromeric SK2-SK3 channels in HEK293 cells. Immunocytochemistry showed that atrial myocytes express both SK2 and SK3 channels with an overlapping expression pattern. Only proposed heteromeric SK2-SK3 channels are physiologically activated to contribute to action potential repolarization, which is indicated by the difference in pharmacology of evoked outward current and prolongation of atrial action potential duration. The effect of blocking this channel on the action potential suggests that SK channel inhibition during cardiac function has the potential to be proarrhythmic. Copyright © 2015 Heart Rhythm Society. Published by Elsevier Inc. All rights reserved.

Urocortin2 prolongs action potential duration and modulates potassium currents in guinea pig myocytes and HEK293 cells.

PubMed

Yang, Li-Zhen; Zhu, Yi-Chun

2015-07-05

We previously reported that activation of corticotropin releasing factor receptor type 2 by urocortin2 up-regulates both L-type Ca(2+) channels and intracellular Ca(2+) concentration in ventricular myocytes and plays an important role in cardiac contractility and arrhythmogenesis. This study goal was to further test the hypothesis that urocortin2 may modulate action potentials as well as rapidly and slowly activating delayed rectifier potassium currents. With whole cell patch-clamp techniques, action potentials and slowly activating delayed rectifier potassium currents were recorded in isolated guinea pig ventricular myocytes, respectively. And rapidly activating delayed rectifier potassium currents were tested in hERG-HEK293 cells. Urocortin2 produced a time- and concentration-dependent prolongation of action potential duration. The EC50 values of action potential duration and action potential duration at 90% of repolarization were 14.73 and 24.3nM respectively. The prolongation of action potential duration of urocortin2 was almost completely or partly abolished by H-89 (protein kinase A inhibitor) or KB-R7943 (Na(+)/Ca(2+) exchange inhibitor) pretreatment respectively. And urocortin2 caused reduction of rapidly activating delayed rectifier potassium currents in hERG-HEK293 cells. In addition, urocortin2 slowed the rate of slowly activating delayed rectifier potassium channel activation, and rightward shifted the threshold of slowly activating delayed rectifier potassium currents to more positive potentials. Urocortin2 prolonged action potential duration via activation of protein kinase A and Na(+)/ Ca(2+) exchange in isolated guinea pig ventricular myocytes in a time- and concentration- dependent manner. In hERG-HEK293 cells, urocortin2 reduced rapidly activating delayed rectifier potassium current density which may contribute to action potential duration prolongation. Copyright © 2015 Elsevier B.V. All rights reserved.

Population of computational rabbit-specific ventricular action potential models for investigating sources of variability in cellular repolarisation.

PubMed

Gemmell, Philip; Burrage, Kevin; Rodriguez, Blanca; Quinn, T Alexander

2014-01-01

Variability is observed at all levels of cardiac electrophysiology. Yet, the underlying causes and importance of this variability are generally unknown, and difficult to investigate with current experimental techniques. The aim of the present study was to generate populations of computational ventricular action potential models that reproduce experimentally observed intercellular variability of repolarisation (represented by action potential duration) and to identify its potential causes. A systematic exploration of the effects of simultaneously varying the magnitude of six transmembrane current conductances (transient outward, rapid and slow delayed rectifier K(+), inward rectifying K(+), L-type Ca(2+), and Na(+)/K(+) pump currents) in two rabbit-specific ventricular action potential models (Shannon et al. and Mahajan et al.) at multiple cycle lengths (400, 600, 1,000 ms) was performed. This was accomplished with distributed computing software specialised for multi-dimensional parameter sweeps and grid execution. An initial population of 15,625 parameter sets was generated for both models at each cycle length. Action potential durations of these populations were compared to experimentally derived ranges for rabbit ventricular myocytes. 1,352 parameter sets for the Shannon model and 779 parameter sets for the Mahajan model yielded action potential duration within the experimental range, demonstrating that a wide array of ionic conductance values can be used to simulate a physiological rabbit ventricular action potential. Furthermore, by using clutter-based dimension reordering, a technique that allows visualisation of multi-dimensional spaces in two dimensions, the interaction of current conductances and their relative importance to the ventricular action potential at different cycle lengths were revealed. Overall, this work represents an important step towards a better understanding of the role that variability in current conductances may play in experimentally observed intercellular variability of rabbit ventricular action potential repolarisation.

Population of Computational Rabbit-Specific Ventricular Action Potential Models for Investigating Sources of Variability in Cellular Repolarisation

PubMed Central

Gemmell, Philip; Burrage, Kevin; Rodriguez, Blanca; Quinn, T. Alexander

2014-01-01

Variability is observed at all levels of cardiac electrophysiology. Yet, the underlying causes and importance of this variability are generally unknown, and difficult to investigate with current experimental techniques. The aim of the present study was to generate populations of computational ventricular action potential models that reproduce experimentally observed intercellular variability of repolarisation (represented by action potential duration) and to identify its potential causes. A systematic exploration of the effects of simultaneously varying the magnitude of six transmembrane current conductances (transient outward, rapid and slow delayed rectifier K+, inward rectifying K+, L-type Ca2+, and Na+/K+ pump currents) in two rabbit-specific ventricular action potential models (Shannon et al. and Mahajan et al.) at multiple cycle lengths (400, 600, 1,000 ms) was performed. This was accomplished with distributed computing software specialised for multi-dimensional parameter sweeps and grid execution. An initial population of 15,625 parameter sets was generated for both models at each cycle length. Action potential durations of these populations were compared to experimentally derived ranges for rabbit ventricular myocytes. 1,352 parameter sets for the Shannon model and 779 parameter sets for the Mahajan model yielded action potential duration within the experimental range, demonstrating that a wide array of ionic conductance values can be used to simulate a physiological rabbit ventricular action potential. Furthermore, by using clutter-based dimension reordering, a technique that allows visualisation of multi-dimensional spaces in two dimensions, the interaction of current conductances and their relative importance to the ventricular action potential at different cycle lengths were revealed. Overall, this work represents an important step towards a better understanding of the role that variability in current conductances may play in experimentally observed intercellular variability of rabbit ventricular action potential repolarisation. PMID:24587229

Action potential propagation: ion current or intramembrane electric field?

PubMed

Martí, Albert; Pérez, Juan J; Madrenas, Jordi

2018-01-01

The established action potential propagation mechanisms do not satisfactorily explain propagation on myelinated axons given the current knowledge of biological channels and membranes. The flow across ion channels presents two possible effects: the electric potential variations across the lipid bilayers (action potential) and the propagation of an electric field through the membrane inner part. The proposed mechanism is based on intra-membrane electric field propagation, this propagation can explain the action potential saltatory propagation and its constant delay independent of distance between Ranvier nodes in myelinated axons.

Antidromic propagation of action potentials in branched axons: implications for the mechanisms of action of deep brain stimulation.

PubMed

Grill, Warren M; Cantrell, Meredith B; Robertson, Matthew S

2008-02-01

Electrical stimulation of the central nervous system creates both orthodromically propagating action potentials, by stimulation of local cells and passing axons, and antidromically propagating action potentials, by stimulation of presynaptic axons and terminals. Our aim was to understand how antidromic action potentials navigate through complex arborizations, such as those of thalamic and basal ganglia afferents-sites of electrical activation during deep brain stimulation. We developed computational models to study the propagation of antidromic action potentials past the bifurcation in branched axons. In both unmyelinated and myelinated branched axons, when the diameters of each axon branch remained under a specific threshold (set by the antidromic geometric ratio), antidromic propagation occurred robustly; action potentials traveled both antidromically into the primary segment as well as "re-orthodromically" into the terminal secondary segment. Propagation occurred across a broad range of stimulation frequencies, axon segment geometries, and concentrations of extracellular potassium, but was strongly dependent on the geometry of the node of Ranvier at the axonal bifurcation. Thus, antidromic activation of axon terminals can, through axon collaterals, lead to widespread activation or inhibition of targets remote from the site of stimulation. These effects should be included when interpreting the results of functional imaging or evoked potential studies on the mechanisms of action of DBS.

Minocycline inhibits D-amphetamine-elicited action potential bursts in a central snail neuron.

PubMed

Chen, Y-H; Lin, P-L; Wong, R-W; Wu, Y-T; Hsu, H-Y; Tsai, M-C; Lin, M-J; Hsu, Y-C; Lin, C-H

2012-10-25

Minocycline is a second-generation tetracycline that has been reported to have powerful neuroprotective properties. In our previous studies, we found that d-amphetamine (AMPH) elicited action potential bursts in an identifiable RP4 neuron of the African snail, Achatina fulica Ferussac. This study sought to determine the effects of minocycline on the AMPH-elicited action potential pattern changes in the central snail neuron, using the two-electrode voltage clamping method. Extracellular application of AMPH at 300 μM elicited action potential bursts in the RP4 neuron. Minocycline dose-dependently (300-900 μM) inhibited the action potential bursts elicited by AMPH. The inhibitory effects of minocycline on AMPH-elicited action potential bursts were restored by forskolin (50 μM), an adenylate cyclase activator, and by dibutyryl cAMP (N(6),2'-O-Dibutyryladenosine 3',5'-cyclic monophosphate; 1mM), a membrane-permeable cAMP analog. Co-administration of forskolin (50 μM) plus tetraethylammonium chloride (TEA; 5mM) or co-administration of TEA (5mM) plus dibutyryl cAMP (1mM) also elicited action potential bursts, which were prevented and inhibited by minocycline. In addition, minocycline prevented and inhibited forskolin (100 μM)-elicited action potential bursts. Notably, TEA (50mM)-elicited action potential bursts in the RP4 neuron were not affected by minocycline. Minocycline did not affect steady-state outward currents of the RP4 neuron. However, minocycline did decrease the AMPH-elicited steady-state current changes. Similarly, minocycline decreased the effects of forskolin-elicited steady-state current changes. Pretreatment with H89 (N-[2-(p-Bromocinnamylamino)ethyl]-5-isoquinolinesulfonamide dihydrochloride; 10 μM), a protein kinase A inhibitor, inhibited AMPH-elicited action potential bursts and decreased AMPH-elicited steady-state current changes. These results suggest that the cAMP-protein kinase A signaling pathway and the steady-state current are involved in the inhibitory effects of minocycline upon AMPH-elicited action potential bursts. Copyright © 2012 IBRO. Published by Elsevier Ltd. All rights reserved.

Selective effects of an octopus toxin on action potentials

PubMed Central

Dulhunty, Angela; Gage, Peter W.

1971-01-01

1. A lethal, water soluble toxin (Maculotoxin, MTX) with a molecular weight less than 540, can be extracted from the salivary glands of an octopus (Hapalochlaena maculosa). 2. MTX blocks action potentials in sartorius muscle fibres of toads without affecting the membrane potential. Delayed rectification is not inhibited by the toxin. 3. At low concentrations (10-6-10-5 g/ml.) MTX blocks action potentials only after a certain number have been elicited. The number of action potentials, which can be defined accurately, depends on the concentration of MTX and the concentration of sodium ions in the extracellular solution. 4. The toxin has no post-synaptic effect at the neuromuscular junction and it is concluded that it blocks neuromuscular transmission by inhibiting action potentials in motor nerve terminals. PMID:4330930

Relationship between size and latency of action potentials in human muscle sympathetic nerve activity.

PubMed

Salmanpour, Aryan; Brown, Lyndon J; Steinback, Craig D; Usselman, Charlotte W; Goswami, Ruma; Shoemaker, J Kevin

2011-06-01

We employed a novel action potential detection and classification technique to study the relationship between the recruitment of sympathetic action potentials (i.e., neurons) and the size of integrated sympathetic bursts in human muscle sympathetic nerve activity (MSNA). Multifiber postganglionic sympathetic nerve activity from the common fibular nerve was collected using microneurography in 10 healthy subjects at rest and during activation of sympathetic outflow using lower body negative pressure (LBNP). Burst occurrence increased with LBNP. Integrated burst strength (size) varied from 0.22 ± 0.07 V at rest to 0.28 ± 0.09 V during LBNP. Sympathetic burst size (i.e., peak height) was directly related to the number of action potentials within a sympathetic burst both at baseline (r = 0.75 ± 0.13; P < 0.001) and LBNP (r = 0.75 ± 0.12; P < 0.001). Also, the amplitude of detected action potentials within sympathetic bursts was directly related to the increased burst size at both baseline (r = 0.59 ± 0.16; P < 0.001) and LBNP (r = 0.61 ± 0.12; P < 0.001). In addition, the number of detected action potentials and the number of distinct action potential clusters within a given sympathetic burst were correlated at baseline (r = 0.7 ± 0.1; P < 0.001) and during LBNP (r = 0.74 ± 0.03; P < 0.001). Furthermore, action potential latency (i.e., an inverse index of neural conduction velocity) was decreased as a function of action potential size at baseline and LBNP. LBNP did not change the number of action potentials and unique clusters per sympathetic burst. It was concluded that there exists a hierarchical pattern of recruitment of additional faster conducting neurons of larger amplitude as the sympathetic bursts become stronger (i.e., larger amplitude bursts). This fundamental pattern was evident at rest and was not altered by the level of baroreceptor unloading applied in this study.

All optical experimental design for neuron excitation, inhibition, and action potential detection

NASA Astrophysics Data System (ADS)

Walsh, Alex J.; Tolstykh, Gleb; Martens, Stacey; Sedelnikova, Anna; Ibey, Bennett L.; Beier, Hope T.

2016-03-01

Recently, infrared light has been shown to both stimulate and inhibit excitatory cells. However, studies of infrared light for excitatory cell inhibition have been constrained by the use of invasive and cumbersome electrodes for cell excitation and action potential recording. Here, we present an all optical experimental design for neuronal excitation, inhibition, and action potential detection. Primary rat neurons were transfected with plasmids containing the light sensitive ion channel CheRiff. CheRiff has a peak excitation around 450 nm, allowing excitation of transfected neurons with pulsed blue light. Additionally, primary neurons were transfected with QuasAr2, a fast and sensitive fluorescent voltage indicator. QuasAr2 is excited with yellow or red light and therefore does not spectrally overlap CheRiff, enabling imaging and action potential activation, simultaneously. Using an optic fiber, neurons were exposed to blue light sequentially to generate controlled action potentials. A second optic fiber delivered a single pulse of 1869nm light to the neuron causing inhibition of the evoked action potentials (by the blue light). When used in concert, these optical techniques enable electrode free neuron excitation, inhibition, and action potential recording, allowing research into neuronal behaviors with high spatial fidelity.

Cortical Action Potential Backpropagation Explains Spike Threshold Variability and Rapid-Onset Kinetics

PubMed Central

Yu, Yuguo; Shu, Yousheng; McCormick, David A.

2008-01-01

Neocortical action potential responses in vivo are characterized by considerable threshold variability, and thus timing and rate variability, even under seemingly identical conditions. This finding suggests that cortical ensembles are required for accurate sensorimotor integration and processing. Intracellularly, trial-to-trial variability results not only from variation in synaptic activities, but also in the transformation of these into patterns of action potentials. Through simultaneous axonal and somatic recordings and computational simulations, we demonstrate that the initiation of action potentials in the axon initial segment followed by backpropagation of these spikes throughout the neuron results in a distortion of the relationship between the timing of synaptic and action potential events. In addition, this backpropagation also results in an unusually high rate of rise of membrane potential at the foot of the action potential. The distortion of the relationship between the amplitude time course of synaptic inputs and action potential output caused by spike back-propagation results in the appearance of high spike threshold variability at the level of the soma. At the point of spike initiation, the axon initial segment, threshold variability is considerably less. Our results indicate that spike generation in cortical neurons is largely as expected by Hodgkin—Huxley theory and is more precise than previously thought. PMID:18632930

Median and ulnar muscle and sensory evoked potentials.

PubMed

Felsenthal, G

1978-08-01

The medical literature was reviewed to find suggested clinical applications of the study of the amplitude of evoked muscle action potentials (MAP) and sensory action potentials (SAP). In addition, the literature was reviewed to ascertain the normal amplitude and duration of the evoked MAP and SAP as well as the factors affecting the amplitude: age, sex, temperature, ischemia. The present study determined the normal amplitude and duration of the median and ulnar MAP and SAP in fifty normal subjects. The amplitude of evoked muscle or sensory action potentials depends on multiple factors. Increased skin resistance, capacitance, and impedance at the surface of the recording electrode diminishes the amplitude. Similarly, increased distance from the source of the action potential diminishes its amplitude. Increased interelectrode distance increases the amplitude of the bipolarly recorded sensory action potential until a certain interelectrode distance is exceeded and the diphasic response becomes tri- or tetraphasic. Artifact or poor technique may reduce the potential difference between the recording electrodes or obscure the late positive phase of the action potential and thus diminish the peak to peak amplitude measurement. Intraindividual comparison indicated a marked difference of amplitude in opposite hands. The range of the MAP of the abductor pollicis brevis in one hand was 40.0--100% of the response in the opposite hand. For the abductor digiti minimi, the MAP was 58.5--100% of the response of the opposite hand. The median and ulnar SAP was between 50--100% of the opposite SAP. Consequent to these findings the effect of hand dominance on the amplitude of median and ulnar evoked muscle and sensory action potentials was studied in 41 right handed volunteers. The amplitudes of the median muscle action potential (p less than 0.02) and the median and ulnar sensory action potentials (p less than 0.001) were significantly less in the dominant hand. There was no significant difference between the ulnar muscle action potentials or for the median and ulnar distal motor and sensory latencies in the right and left hands of this group of volunteers.

Ionotropic glutamate receptor GluA4 and T-type calcium channel Cav 3.1 subunits control key aspects of synaptic transmission at the mouse L5B-POm giant synapse.

PubMed

Seol, Min; Kuner, Thomas

2015-12-01

The properties and molecular determinants of synaptic transmission at giant synapses connecting layer 5B (L5B) neurons of the somatosensory cortex (S1) with relay neurons of the posteriomedial nucleus (POm) of the thalamus have not been investigated in mice. We addressed this by using direct electrical stimulation of fluorescently labelled single corticothalamic terminals combined with molecular perturbations and whole-cell recordings from POm relay neurons. Consistent with their function as drivers, we found large-amplitude excitatory postsynaptic currents (EPSCs) and multiple postsynaptic action potentials triggered by a single presynaptic action potential. To study the molecular basis of these two features, ionotropic glutamate receptors and low voltage-gated T-type calcium channels were probed by virus-mediated genetic perturbation. Loss of GluA4 almost abolished the EPSC amplitude, strongly delaying the onset of action potential generation, but maintaining the number of action potentials generated per presynaptic action potential. In contrast, knockdown of the Cav 3.1 subunit abrogated the driver function of the synapse at a typical resting membrane potential of -70 mV. However, when depolarizing the membrane potential to -60 mV, the synapse relayed single action potentials. Hence, GluA4 subunits are required to produce an EPSC sufficiently large to trigger postsynaptic action potentials within a defined time window after the presynaptic action potential, while Cav 3.1 expression is essential to establish the driver function of L5B-POm synapses at hyperpolarized membrane potentials. © 2015 The Authors. European Journal of Neuroscience published by Federation of European Neuroscience Societies and John Wiley & Sons Ltd.

Low concentrations of procaine and diethylaminoethanol reduce the excitability but not the action potential amplitude of hippocampal pyramidal cells.

PubMed

Butterworth, J F; Cole, L R

1990-10-01

To determine whether concentrations of diethylaminoethanol (DEAE) and procaine below those that reduce the amplitude of action potentials might alter the excitability of brain cells, a single microelectrode intracellular recording technique was used to measure firing threshold and action potential amplitude of pyramidal cells in rat hippocampal slices. At low concentrations of both DEAE (less than or equal to 5 mM) and procaine (less than or equal to 0.5 mM), firing threshold was significantly increased (P less than 0.01), whereas action potential spike amplitude was minimally altered. At higher concentrations, both drugs significantly decreased action potential spike amplitude (P less than 0.025) as well as increased firing threshold (P less than 0.001). Diethylaminoethanol tended to increase threshold relatively more than procaine, when drug concentrations that similarly reduced action potential amplitude were compared. All actions of DEAE and procaine were reversible. Inhibition of action potentials by DEAE and procaine was clearly concentration-dependent (P less than or equal to 0.015). Diethylaminoethanol effects on threshold were marginally concentration-dependent (P = 0.08); procaine did not demonstrate clear concentration-dependent effects (P = 0.33) over the concentrations tested in this study. These similar actions of procaine and DEAE on brain cells suggest a mechanism by which intravenous local anesthetics may contribute to the general anesthetic state. Moreover, it appears possible that procaine metabolism and DEAE accumulation may underlie the prolonged effects sometimes seen after intravenous procaine administration.

78 FR 34031 - Burned Area Emergency Response, Forest Service

Federal Register 2010, 2011, 2012, 2013, 2014

2013-06-06

...) Evaluate potential threats to critical values; (2) determine the risk level for each threat; (3) identify... actions that meet the objectives; (6) evaluate potential response actions on likelihood for timely... stabilization actions. Improved the descriptive guidelines for employing response actions involving...

Conduction velocity of action potentials measured from unidimensional latency-topography in human and frog skeletal muscle fibers.

PubMed

Homma, S; Nakajima, Y; Hayashi, K; Toma, S

1986-01-01

Conduction of an action potential along skeletal muscle fibers was graphically displayed by unidimensional latency-topography, UDLT. Since the slopes of the equipotential line were linear and the width of the line was constant, it was possible to calculate conduction velocity from the slope. To determine conduction direction of the muscle action potential elicited by electric stimulation applied directly to the muscle, surface recording electrodes were placed on a two-dimensional plane over a human muscle. Thus a bi-dimensional topography was obtained. Then, twelve or sixteen surface electrodes were placed linearly along the longitudinal direction of the action potential conduction which was disclosed by the bi-dimensional topography. Thus conduction velocity of muscle action potential in man, calculated from the slope, was for m. brachioradialis, 3.9 +/- 0.4 m/s; for m. biceps brachii, 3.6 +/- 0.2 m/s; for m. sternocleidomastoideus, 3.6 +/- 0.4 m/s. By using a tungsten microelectrode to stimulate the motor axons, a convex-like equipotential line of an action potential in UDLT was obtained from human muscle fibers. Since a similar pattern of UDLT was obtained from experiments on isolated frog muscles, in which the muscle action potential was elicited by stimulating the motor axon, it was assumed that the maximum of the curve corresponds to the end-plate region, and that the slopes on both sides indicate bi-directional conduction of the action potential.

Active action potential propagation but not initiation in thalamic interneuron dendrites

PubMed Central

Casale, Amanda E.; McCormick, David A.

2012-01-01

Inhibitory interneurons of the dorsal lateral geniculate nucleus of the thalamus modulate the activity of thalamocortical cells in response to excitatory input through the release of inhibitory neurotransmitter from both axons and dendrites. The exact mechanisms by which release can occur from dendrites are, however, not well understood. Recent experiments using calcium imaging have suggested that Na/K based action potentials can evoke calcium transients in dendrites via local active conductances, making the back-propagating action potential a candidate for dendritic neurotransmitter release. In this study, we employed high temporal and spatial resolution voltage-sensitive dye imaging to assess the characteristics of dendritic voltage deflections in response to Na/K action potentials in interneurons of the mouse dorsal lateral geniculate nucleus. We found that trains or single action potentials elicited by somatic current injection or local synaptic stimulation led to action potentials that rapidly and actively back-propagated throughout the entire dendritic arbor and into the fine filiform dendritic appendages known to release GABAergic vesicles. Action potentials always appeared first in the soma or proximal dendrite in response to somatic current injection or local synaptic stimulation, and the rapid back-propagation into the dendritic arbor depended upon voltage-gated sodium and TEA-sensitive potassium channels. Our results indicate that thalamic interneuron dendrites integrate synaptic inputs that initiate action potentials, most likely in the axon initial segment, that then back-propagate with high-fidelity into the dendrites, resulting in a nearly synchronous release of GABA from both axonal and dendritic compartments. PMID:22171033

Event-Related Potentials Discriminate Familiar and Unusual Goal Outcomes in 5-Month-Olds and Adults

ERIC Educational Resources Information Center

Michel, Christine; Kaduk, Katharina; Ní Choisdealbha, Áine; Reid, Vincent M.

2017-01-01

Previous event-related potential (ERP) work has indicated that the neural processing of action sequences develops with age. Although adults and 9-month-olds use a semantic processing system, perceiving actions activates attentional processes in 7-month-olds. However, presenting a sequence of action context, action execution and action conclusion…

Understanding the Electrical Behavior of the Action Potential in Terms of Elementary Electrical Sources

ERIC Educational Resources Information Center

Rodriguez-Falces, Javier

2015-01-01

A concept of major importance in human electrophysiology studies is the process by which activation of an excitable cell results in a rapid rise and fall of the electrical membrane potential, the so-called action potential. Hodgkin and Huxley proposed a model to explain the ionic mechanisms underlying the formation of action potentials. However,…

Detachable glass microelectrodes for recording action potentials in active moving organs.

PubMed

Barbic, Mladen; Moreno, Angel; Harris, Tim D; Kay, Matthew W

2017-06-01

Here, we describe new detachable floating glass micropipette electrode devices that provide targeted action potential recordings in active moving organs without requiring constant mechanical constraint or pharmacological inhibition of tissue motion. The technology is based on the concept of a glass micropipette electrode that is held firmly during cell targeting and intracellular insertion, after which a 100-µg glass microelectrode, a "microdevice," is gently released to remain within the moving organ. The microdevices provide long-term recordings of action potentials, even during millimeter-scale movement of tissue in which the device is embedded. We demonstrate two different glass micropipette electrode holding and detachment designs appropriate for the heart (sharp glass microdevices for cardiac myocytes in rats, guinea pigs, and humans) and the brain (patch glass microdevices for neurons in rats). We explain how microdevices enable measurements of multiple cells within a moving organ that are typically difficult with other technologies. Using sharp microdevices, action potential duration was monitored continuously for 15 min in unconstrained perfused hearts during global ischemia-reperfusion, providing beat-to-beat measurements of changes in action potential duration. Action potentials from neurons in the hippocampus of anesthetized rats were measured with patch microdevices, which provided stable base potentials during long-term recordings. Our results demonstrate that detachable microdevices are an elegant and robust tool to record electrical activity with high temporal resolution and cellular level localization without disturbing the physiological working conditions of the organ. NEW & NOTEWORTHY Cellular action potential measurements within tissue using glass micropipette electrodes usually require tissue immobilization, potentially influencing the physiological relevance of the measurement. Here, we addressed this limitation with novel 100-µg detachable glass microelectrodes that can be precisely positioned to provide long-term measurements of action potential duration during unconstrained tissue movement. Copyright © 2017 the American Physiological Society.

Are Current Atomistic Force Fields Accurate Enough to Study Proteins in Crowded Environments?

PubMed Central

Petrov, Drazen; Zagrovic, Bojan

2014-01-01

The high concentration of macromolecules in the crowded cellular interior influences different thermodynamic and kinetic properties of proteins, including their structural stabilities, intermolecular binding affinities and enzymatic rates. Moreover, various structural biology methods, such as NMR or different spectroscopies, typically involve samples with relatively high protein concentration. Due to large sampling requirements, however, the accuracy of classical molecular dynamics (MD) simulations in capturing protein behavior at high concentration still remains largely untested. Here, we use explicit-solvent MD simulations and a total of 6.4 µs of simulated time to study wild-type (folded) and oxidatively damaged (unfolded) forms of villin headpiece at 6 mM and 9.2 mM protein concentration. We first perform an exhaustive set of simulations with multiple protein molecules in the simulation box using GROMOS 45a3 and 54a7 force fields together with different types of electrostatics treatment and solution ionic strengths. Surprisingly, the two villin headpiece variants exhibit similar aggregation behavior, despite the fact that their estimated aggregation propensities markedly differ. Importantly, regardless of the simulation protocol applied, wild-type villin headpiece consistently aggregates even under conditions at which it is experimentally known to be soluble. We demonstrate that aggregation is accompanied by a large decrease in the total potential energy, with not only hydrophobic, but also polar residues and backbone contributing substantially. The same effect is directly observed for two other major atomistic force fields (AMBER99SB-ILDN and CHARMM22-CMAP) as well as indirectly shown for additional two (AMBER94, OPLS-AAL), and is possibly due to a general overestimation of the potential energy of protein-protein interactions at the expense of water-water and water-protein interactions. Overall, our results suggest that current MD force fields may distort the picture of protein behavior in biologically relevant crowded environments. PMID:24854339

Corneal confocal microscopy detects small fiber neuropathy in CMT1A patients

PubMed Central

Tavakoli, Mitra; Marshall, Andy; Banka, Siddharth; Petropoulos, Ioannis N; Fadavi, Hassan; Kingston, Helen; Malik, Rayaz A

2012-01-01

Although unmyelinated nerve fibers are affected in CMT1A, they have not been studied in detail due to the invasive nature of the techniques needed to study them. We established alterations in C-fiber bundles of the cornea in patients with CMT1A using non-invasive corneal confocal microscopy (CCM). Twelve patients with CMT1A and twelve healthy control subjects underwent assessment of neuropathic symptoms and deficits, electrophysiology, quantitative sensory testing, corneal sensitivity and corneal confocal microscopy. Corneal sensitivity, corneal nerve fiber density, corneal nerve branch density, corneal nerve fiber length and corneal nerve fiber tortuosity were significantly reduced in CMT1A patients compared to controls. There was a significant correlation between corneal sensation and CCM parameters with the severity of painful neuropathic symptoms, cold and warm thresholds and median nerve CMAP amplitude. CCM demonstrates significant damage to C-fiber bundles, which relates to some measures of neuropathy in CMT1A patients. PMID:22996176

Integrated analysis of drug-induced gene expression profiles predicts novel hERG inhibitors.

PubMed

Babcock, Joseph J; Du, Fang; Xu, Kaiping; Wheelan, Sarah J; Li, Min

2013-01-01

Growing evidence suggests that drugs interact with diverse molecular targets mediating both therapeutic and toxic effects. Prediction of these complex interactions from chemical structures alone remains challenging, as compounds with different structures may possess similar toxicity profiles. In contrast, predictions based on systems-level measurements of drug effect may reveal pharmacologic similarities not evident from structure or known therapeutic indications. Here we utilized drug-induced transcriptional responses in the Connectivity Map (CMap) to discover such similarities among diverse antagonists of the human ether-à-go-go related (hERG) potassium channel, a common target of promiscuous inhibition by small molecules. Analysis of transcriptional profiles generated in three independent cell lines revealed clusters enriched for hERG inhibitors annotated using a database of experimental measurements (hERGcentral) and clinical indications. As a validation, we experimentally identified novel hERG inhibitors among the unannotated drugs in these enriched clusters, suggesting transcriptional responses may serve as predictive surrogates of cardiotoxicity complementing existing functional assays.

Case-Based Capture and Reuse of Aerospace Design Rationale

NASA Technical Reports Server (NTRS)

Leake, David B.

2001-01-01

The goal of this project was to apply artificial intelligence techniques to facilitate capture and reuse of aerospace design rationale. The project combined case-based reasoning (CBR) and concept maps (CMaps) to develop methods for capturing, organizing, and interactively accessing records of experiences encapsulating the methods and rationale underlying expert aerospace design, in order to bring the captured knowledge to bear to support future reasoning. The project's results contribute both principles and methods for effective design-aiding systems that aid capture and access of useful design knowledge. The project has been guided by the tenets that design-aiding systems must: (1) Leverage a designer's knowledge, rather than attempting to replace it; (2) Be able to reflect different designers' differing conceptualizations of the design task, and to clarify those conceptualizations to others; (3) Include capabilities to capture information both by interactive knowledge modeling and during normal use; and (4) Integrate into normal designer tasks as naturally and unobtrusive as possible.

Integrated Analysis of Drug-Induced Gene Expression Profiles Predicts Novel hERG Inhibitors

PubMed Central

Babcock, Joseph J.; Du, Fang; Xu, Kaiping; Wheelan, Sarah J.; Li, Min

2013-01-01

Growing evidence suggests that drugs interact with diverse molecular targets mediating both therapeutic and toxic effects. Prediction of these complex interactions from chemical structures alone remains challenging, as compounds with different structures may possess similar toxicity profiles. In contrast, predictions based on systems-level measurements of drug effect may reveal pharmacologic similarities not evident from structure or known therapeutic indications. Here we utilized drug-induced transcriptional responses in the Connectivity Map (CMap) to discover such similarities among diverse antagonists of the human ether-à-go-go related (hERG) potassium channel, a common target of promiscuous inhibition by small molecules. Analysis of transcriptional profiles generated in three independent cell lines revealed clusters enriched for hERG inhibitors annotated using a database of experimental measurements (hERGcentral) and clinical indications. As a validation, we experimentally identified novel hERG inhibitors among the unannotated drugs in these enriched clusters, suggesting transcriptional responses may serve as predictive surrogates of cardiotoxicity complementing existing functional assays. PMID:23936032

Quadratic adaptive algorithm for solving cardiac action potential models.

PubMed

Chen, Min-Hung; Chen, Po-Yuan; Luo, Ching-Hsing

2016-10-01

An adaptive integration method is proposed for computing cardiac action potential models accurately and efficiently. Time steps are adaptively chosen by solving a quadratic formula involving the first and second derivatives of the membrane action potential. To improve the numerical accuracy, we devise an extremum-locator (el) function to predict the local extremum when approaching the peak amplitude of the action potential. In addition, the time step restriction (tsr) technique is designed to limit the increase in time steps, and thus prevent the membrane potential from changing abruptly. The performance of the proposed method is tested using the Luo-Rudy phase 1 (LR1), dynamic (LR2), and human O'Hara-Rudy dynamic (ORd) ventricular action potential models, and the Courtemanche atrial model incorporating a Markov sodium channel model. Numerical experiments demonstrate that the action potential generated using the proposed method is more accurate than that using the traditional Hybrid method, especially near the peak region. The traditional Hybrid method may choose large time steps near to the peak region, and sometimes causes the action potential to become distorted. In contrast, the proposed new method chooses very fine time steps in the peak region, but large time steps in the smooth region, and the profiles are smoother and closer to the reference solution. In the test on the stiff Markov ionic channel model, the Hybrid blows up if the allowable time step is set to be greater than 0.1ms. In contrast, our method can adjust the time step size automatically, and is stable. Overall, the proposed method is more accurate than and as efficient as the traditional Hybrid method, especially for the human ORd model. The proposed method shows improvement for action potentials with a non-smooth morphology, and it needs further investigation to determine whether the method is helpful during propagation of the action potential. Copyright © 2016 Elsevier Ltd. All rights reserved.

Effects of tacrolimus on action potential configuration and transmembrane ion currents in canine ventricular cells.

PubMed

Szabó, László; Szentandrássy, Norbert; Kistamás, Kornél; Hegyi, Bence; Ruzsnavszky, Ferenc; Váczi, Krisztina; Horváth, Balázs; Magyar, János; Bányász, Tamás; Pál, Balázs; Nánási, Péter P

2013-03-01

Tacrolimus is a commonly used immunosuppressive agent which causes cardiovascular complications, e.g., hypertension and hypertrophic cardiomyopathy. In spite of it, there is little information on the cellular cardiac effects of the immunosuppressive agent tacrolimus in larger mammals. In the present study, therefore, the concentration-dependent effects of tacrolimus on action potential morphology and the underlying ion currents were studied in canine ventricular cardiomyocytes. Standard microelectrode, conventional whole cell patch clamp, and action potential voltage clamp techniques were applied in myocytes enzymatically dispersed from canine ventricular myocardium. Tacrolimus (3-30 μM) caused a concentration-dependent reduction of maximum velocity of depolarization and repolarization, action potential amplitude, phase-1 repolarization, action potential duration, and plateau potential, while no significant change in the resting membrane potential was observed. Conventional voltage clamp experiments revealed that tacrolimus concentrations ≥3 μM blocked a variety of ion currents, including I(Ca), I(to), I(K1), I(Kr), and I(Ks). Similar results were obtained under action potential voltage clamp conditions. These effects of tacrolimus developed rapidly and were fully reversible upon washout. The blockade of inward currents with the concomitant shortening of action potential duration in canine myocytes is the opposite of those observed previously with tacrolimus in small rodents. It is concluded that although tacrolimus blocks several ion channels at higher concentrations, there is no risk of direct interaction with cardiac ion channels when applying tacrolimus in therapeutic concentrations.

TRPM4 non-selective cation channels influence action potentials in rabbit Purkinje fibres.

PubMed

Hof, Thomas; Sallé, Laurent; Coulbault, Laurent; Richer, Romain; Alexandre, Joachim; Rouet, René; Manrique, Alain; Guinamard, Romain

2016-01-15

The transient receptor potential melastatin 4 (TRPM4) inhibitor 9-phenanthrol reduces action potential duration in rabbit Purkinje fibres but not in ventricle. TRPM4-like single channel activity is observed in isolated rabbit Purkinje cells but not in ventricular cells. The TRPM4-like current develops during the notch and early repolarization phases of the action potential in Purkinje cells. Transient receptor potential melastatin 4 (TRPM4) Ca(2+)-activated non-selective cation channel activity has been recorded in cardiomyocytes and sinus node cells from mammals. In addition, TRPM4 gene mutations are associated with human diseases of cardiac conduction, suggesting that TRPM4 plays a role in this aspect of cardiac function. Here we evaluate the TRPM4 contribution to cardiac electrophysiology of Purkinje fibres. Ventricular strips with Purkinje fibres were isolated from rabbit hearts. Intracellular microelectrodes recorded Purkinje fibre activity and the TRPM4 inhibitor 9-phenanthrol was applied to unmask potential TRPM4 contributions to the action potential. 9-Phenanthrol reduced action potential duration measured at the point of 50 and 90% repolarization with an EC50 of 32.8 and 36.1×10(-6) mol l(-1), respectively, but did not modulate ventricular action potentials. Inside-out patch-clamp recordings were used to monitor TRPM4 activity in isolated Purkinje cells. TRPM4-like single channel activity (conductance = 23.8 pS; equal permeability for Na(+) and K(+); sensitivity to voltage, Ca(2+) and 9-phenanthrol) was observed in 43% of patches from Purkinje cells but not from ventricular cells (0/16). Action potential clamp experiments performed in the whole-cell configuration revealed a transient inward 9-phenanthrol-sensitive current (peak density = -0.65 ± 0.15 pA pF(-1); n = 5) during the plateau phases of the Purkinje fibre action potential. These results show that TRPM4 influences action potential characteristics in rabbit Purkinje fibres and thus could modulate cardiac conduction and be involved in triggering arrhythmias. © 2015 The Authors. The Journal of Physiology © 2015 The Physiological Society.

14 CFR 1216.306 - Actions normally requiring an EIS.

Code of Federal Regulations, 2013 CFR

2013-01-01

... normally requiring an EIS. (a) NASA will prepare an EIS for actions with the potential to significantly... action or mitigation of its potentially significant impacts. (b) Typical NASA actions normally requiring... material greater than the quantity for which the NASA Nuclear Flight Safety Assurance Manager may grant...

Cell-type-dependent action potentials and voltage-gated currents in mouse fungiform taste buds.

PubMed

Kimura, Kenji; Ohtubo, Yoshitaka; Tateno, Katsumi; Takeuchi, Keita; Kumazawa, Takashi; Yoshii, Kiyonori

2014-01-01

Taste receptor cells fire action potentials in response to taste substances to trigger non-exocytotic neurotransmitter release in type II cells and exocytotic release in type III cells. We investigated possible differences between these action potentials fired by mouse taste receptor cells using in situ whole-cell recordings, and subsequently we identified their cell types immunologically with cell-type markers, an IP3 receptor (IP3 R3) for type II cells and a SNARE protein (SNAP-25) for type III cells. Cells not immunoreactive to these antibodies were examined as non-IRCs. Here, we show that type II cells and type III cells fire action potentials using different ionic mechanisms, and that non-IRCs also fire action potentials with either of the ionic mechanisms. The width of action potentials was significantly narrower and their afterhyperpolarization was deeper in type III cells than in type II cells. Na(+) current density was similar in type II cells and type III cells, but it was significantly smaller in non-IRCs than in the others. Although outwardly rectifying current density was similar between type II cells and type III cells, tetraethylammonium (TEA) preferentially suppressed the density in type III cells and the majority of non-IRCs. Our mathematical model revealed that the shape of action potentials depended on the ratio of TEA-sensitive current density and TEA-insensitive current one. The action potentials of type II cells and type III cells under physiological conditions are discussed. © 2013 Federation of European Neuroscience Societies and John Wiley & Sons Ltd.

The optimal distance between two electrode tips during recording of compound nerve action potentials in the rat median nerve

PubMed Central

Li, Yongping; Lao, Jie; Zhao, Xin; Tian, Dong; Zhu, Yi; Wei, Xiaochun

2014-01-01

The distance between the two electrode tips can greatly influence the parameters used for recording compound nerve action potentials. To investigate the optimal parameters for these recordings in the rat median nerve, we dissociated the nerve using different methods and compound nerve action potentials were orthodromically or antidromically recorded with different electrode spacings. Compound nerve action potentials could be consistently recorded using a method in which the middle part of the median nerve was intact, with both ends dissociated from the surrounding fascia and a ground wire inserted into the muscle close to the intact part. When the distance between two stimulating electrode tips was increased, the threshold and supramaximal stimulating intensity of compound nerve action potentials were gradually decreased, but the amplitude was not changed significantly. When the distance between two recording electrode tips was increased, the amplitude was gradually increased, but the threshold and supramaximal stimulating intensity exhibited no significant change. Different distances between recording and stimulating sites did not produce significant effects on the aforementioned parameters. A distance of 5 mm between recording and stimulating electrodes and a distance of 10 mm between recording and stimulating sites were found to be optimal for compound nerve action potential recording in the rat median nerve. In addition, the orthodromic compound action potential, with a biphasic waveform that was more stable and displayed less interference (however also required a higher threshold and higher supramaximal stimulus), was found to be superior to the antidromic compound action potential. PMID:25206798

Modulation of hERG potassium channel gating normalizes action potential duration prolonged by dysfunctional KCNQ1 potassium channel

PubMed Central

Zhang, Hongkang; Zou, Beiyan; Yu, Haibo; Moretti, Alessandra; Wang, Xiaoying; Yan, Wei; Babcock, Joseph J.; Bellin, Milena; McManus, Owen B.; Tomaselli, Gordon; Nan, Fajun; Laugwitz, Karl-Ludwig; Li, Min

2012-01-01

Long QT syndrome (LQTS) is a genetic disease characterized by a prolonged QT interval in an electrocardiogram (ECG), leading to higher risk of sudden cardiac death. Among the 12 identified genes causal to heritable LQTS, ∼90% of affected individuals harbor mutations in either KCNQ1 or human ether-a-go-go related genes (hERG), which encode two repolarizing potassium currents known as IKs and IKr. The ability to quantitatively assess contributions of different current components is therefore important for investigating disease phenotypes and testing effectiveness of pharmacological modulation. Here we report a quantitative analysis by simulating cardiac action potentials of cultured human cardiomyocytes to match the experimental waveforms of both healthy control and LQT syndrome type 1 (LQT1) action potentials. The quantitative evaluation suggests that elevation of IKr by reducing voltage sensitivity of inactivation, not via slowing of deactivation, could more effectively restore normal QT duration if IKs is reduced. Using a unique specific chemical activator for IKr that has a primary effect of causing a right shift of V1/2 for inactivation, we then examined the duration changes of autonomous action potentials from differentiated human cardiomyocytes. Indeed, this activator causes dose-dependent shortening of the action potential durations and is able to normalize action potentials of cells of patients with LQT1. In contrast, an IKr chemical activator of primary effects in slowing channel deactivation was not effective in modulating action potential durations. Our studies provide both the theoretical basis and experimental support for compensatory normalization of action potential duration by a pharmacological agent. PMID:22745159

Short infrared laser pulses block action potentials in neurons

NASA Astrophysics Data System (ADS)

Walsh, Alex J.; Tolstykh, Gleb P.; Martens, Stacey L.; Ibey, Bennett L.; Beier, Hope T.

2017-02-01

Short infrared laser pulses have many physiological effects on cells including the ability to stimulate action potentials in neurons. Here we show that short infrared laser pulses can also reversibly block action potentials. Primary rat hippocampal neurons were transfected with the Optopatch2 plasmid, which contains both a blue-light activated channel rhodopsin (CheRiff) and a red-light fluorescent membrane voltage reporter (QuasAr2). This optogenetic platform allows robust stimulation and recording of action potential activity in neurons in a non-contact, low noise manner. For all experiments, QuasAr2 was imaged continuously on a wide-field fluorescent microscope using a Krypton laser (647 nm) as the excitation source and an EMCCD camera operating at 1000 Hz to collect emitted fluorescence. A co-aligned Argon laser (488 nm, 5 ms at 10Hz) provided activation light for CheRiff. A 200 mm fiber delivered infrared light locally to the target neuron. Reversible action potential block in neurons was observed following a short infrared laser pulse (0.26-0.96 J/cm2; 1.37-5.01 ms; 1869 nm), with the block persisting for more than 1 s with exposures greater than 0.69 J/cm2. Action potential block was sustained for 30 s with the short infrared laser pulsed at 1-7 Hz. Full recovery of neuronal activity was observed 5-30s post-infrared exposure. These results indicate that optogenetics provides a robust platform for the study of action potential block and that short infrared laser pulses can be used for non-contact, reversible action potential block.

Action potentials and ion conductances in wild-type and CALHM1-knockout type II taste cells

PubMed Central

Saung, Wint Thu; Foskett, J. Kevin

2017-01-01

Taste bud type II cells fire action potentials in response to tastants, triggering nonvesicular ATP release to gustatory neurons via voltage-gated CALHM1-associated ion channels. Whereas CALHM1 regulates mouse cortical neuron excitability, its roles in regulating type II cell excitability are unknown. In this study, we compared membrane conductances and action potentials in single identified TRPM5-GFP-expressing circumvallate papillae type II cells acutely isolated from wild-type (WT) and Calhm1 knockout (KO) mice. The activation kinetics of large voltage-gated outward currents were accelerated in cells from Calhm1 KO mice, and their associated nonselective tail currents, previously shown to be highly correlated with ATP release, were completely absent in Calhm1 KO cells, suggesting that CALHM1 contributes to all of these currents. Calhm1 deletion did not significantly alter resting membrane potential or input resistance, the amplitudes and kinetics of Na+ currents either estimated from action potentials or recorded from steady-state voltage pulses, or action potential threshold, overshoot peak, afterhyperpolarization, and firing frequency. However, Calhm1 deletion reduced the half-widths of action potentials and accelerated the deactivation kinetics of transient outward currents, suggesting that the CALHM1-associated conductance becomes activated during the repolarization phase of action potentials. NEW & NOTEWORTHY CALHM1 is an essential ion channel component of the ATP neurotransmitter release mechanism in type II taste bud cells. Its contribution to type II cell resting membrane properties and excitability is unknown. Nonselective voltage-gated currents, previously associated with ATP release, were absent in cells lacking CALHM1. Calhm1 deletion was without effects on resting membrane properties or voltage-gated Na+ and K+ channels but contributed modestly to the kinetics of action potentials. PMID:28202574

Somatic spikes regulate dendritic signaling in small neurons in the absence of backpropagating action potentials.

PubMed

Myoga, Michael H; Beierlein, Michael; Regehr, Wade G

2009-06-17

Somatic spiking is known to regulate dendritic signaling and associative synaptic plasticity in many types of large neurons, but it is unclear whether somatic action potentials play similar roles in small neurons. Here we ask whether somatic action potentials can also influence dendritic signaling in an electrically compact neuron, the cerebellar stellate cell (SC). Experiments were conducted in rat brain slices using a combination of imaging and electrophysiology. We find that somatic action potentials elevate dendritic calcium levels in SCs. There was little attenuation of calcium signals with distance from the soma in SCs from postnatal day 17 (P17)-P19 rats, which had dendrites that averaged 60 microm in length, and in short SC dendrites from P30-P33 rats. Somatic action potentials evoke dendritic calcium increases that are not affected by blocking dendritic sodium channels. This indicates that dendritic signals in SCs do not rely on dendritic sodium channels, which differs from many types of large neurons, in which dendritic sodium channels and backpropagating action potentials allow somatic spikes to control dendritic calcium signaling. Despite the lack of active backpropagating action potentials, we find that trains of somatic action potentials elevate dendritic calcium sufficiently to release endocannabinoids and retrogradely suppress parallel fiber to SC synapses in P17-P19 rats. Prolonged SC firing at physiologically realistic frequencies produces retrograde suppression when combined with low-level group I metabotropic glutamate receptor activation. Somatic spiking also interacts with synaptic stimulation to promote associative plasticity. These findings indicate that in small neurons the passive spread of potential within dendrites can allow somatic spiking to regulate dendritic calcium signaling and synaptic plasticity.

Action potentials and ion conductances in wild-type and CALHM1-knockout type II taste cells.

PubMed

Ma, Zhongming; Saung, Wint Thu; Foskett, J Kevin

2017-05-01

Taste bud type II cells fire action potentials in response to tastants, triggering nonvesicular ATP release to gustatory neurons via voltage-gated CALHM1-associated ion channels. Whereas CALHM1 regulates mouse cortical neuron excitability, its roles in regulating type II cell excitability are unknown. In this study, we compared membrane conductances and action potentials in single identified TRPM5-GFP-expressing circumvallate papillae type II cells acutely isolated from wild-type (WT) and Calhm1 knockout (KO) mice. The activation kinetics of large voltage-gated outward currents were accelerated in cells from Calhm1 KO mice, and their associated nonselective tail currents, previously shown to be highly correlated with ATP release, were completely absent in Calhm1 KO cells, suggesting that CALHM1 contributes to all of these currents. Calhm1 deletion did not significantly alter resting membrane potential or input resistance, the amplitudes and kinetics of Na + currents either estimated from action potentials or recorded from steady-state voltage pulses, or action potential threshold, overshoot peak, afterhyperpolarization, and firing frequency. However, Calhm1 deletion reduced the half-widths of action potentials and accelerated the deactivation kinetics of transient outward currents, suggesting that the CALHM1-associated conductance becomes activated during the repolarization phase of action potentials. NEW & NOTEWORTHY CALHM1 is an essential ion channel component of the ATP neurotransmitter release mechanism in type II taste bud cells. Its contribution to type II cell resting membrane properties and excitability is unknown. Nonselective voltage-gated currents, previously associated with ATP release, were absent in cells lacking CALHM1. Calhm1 deletion was without effects on resting membrane properties or voltage-gated Na + and K + channels but contributed modestly to the kinetics of action potentials. Copyright © 2017 the American Physiological Society.

The activity of spontaneous action potentials in developing hair cells is regulated by Ca(2+)-dependence of a transient K+ current.

PubMed

Levic, Snezana; Lv, Ping; Yamoah, Ebenezer N

2011-01-01

Spontaneous action potentials have been described in developing sensory systems. These rhythmic activities may have instructional roles for the functional development of synaptic connections. The importance of spontaneous action potentials in the developing auditory system is underpinned by the stark correlation between the time of auditory system functional maturity, and the cessation of spontaneous action potentials. A prominent K(+) current that regulates patterning of action potentials is I(A). This current undergoes marked changes in expression during chicken hair cell development. Although the properties of I(A) are not normally classified as Ca(2+)-dependent, we demonstrate that throughout the development of chicken hair cells, I(A) is greatly reduced by acute alterations of intracellular Ca(2+). As determinants of spike timing and firing frequency, intracellular Ca(2+) buffers shift the activation and inactivation properties of the current to more positive potentials. Our findings provide evidence to demonstrate that the kinetics and functional expression of I(A) are tightly regulated by intracellular Ca(2+). Such feedback mechanism between the functional expression of I(A) and intracellular Ca(2+) may shape the activity of spontaneous action potentials, thus potentially sculpting synaptic connections in an activity-dependent manner in the developing cochlea. © 2011 Levic et al.

78 FR 23740 - Notice of Availability of a Swine Brucellosis and Pseudorabies Proposed Action Plan

Federal Register 2010, 2011, 2012, 2013, 2014

2013-04-22

...] Notice of Availability of a Swine Brucellosis and Pseudorabies Proposed Action Plan AGENCY: Animal and... proposed action plan describing a potential new approach to managing swine brucellosis and pseudorabies...-0086) a notice that made a proposed action plan describing a potential new approach to managing swine...

Modulating anosognosia for hemiplegia: The role of dangerous actions in emergent awareness.

PubMed

D'Imperio, Daniela; Bulgarelli, Cristina; Bertagnoli, Sara; Avesani, Renato; Moro, Valentina

2017-07-01

Anosognosia for hemiplegia is a lack of awareness of motor deficits following a right hemisphere lesion. Residual forms of awareness co-occur with an explicit denial of hemiplegia. The term emergent awareness refers to a condition in which awareness of motor deficits is reported verbally during the actual performance of an action involving the affected body part. In this study, two tasks were used to explore the potential effects of i) attempting actions which are impossible for sufferers of hemiplegia and ii) attempting actions which are potentially dangerous. Sixteen hemiplegic patients (8 anosognosic, and 8 non-anosognosic) were asked to perform both potentially dangerous and neutral actions. Our results confirm an increase in emergent awareness in anosognosic patients during the execution of both of these types of action. Moreover, actions that are potentially dangerous improved the degree of awareness. However, lesions in the fronto-temporal areas appear to be associated with a reduced effect of action execution (emergent awareness) while lesions in the basal ganglia and amygdale and the white matter underlying the insula and fronto-temporal areas are associated with a lesser degree of improvement resulting from attempting to perform dangerous actions. Copyright © 2017 Elsevier Ltd. All rights reserved.

[Effect of pulse magnetic field on distribution of neuronal action potential].

PubMed

Zheng, Yu; Cai, Di; Wang, Jin-Hai; Li, Gang; Lin, Ling

2014-08-25

The biological effect on the organism generated by magnetic field is widely studied. The present study was aimed to observe the change of sodium channel under magnetic field in neurons. Cortical neurons of Kunming mice were isolated, subjected to 15 Hz, 1 mT pulse magnetic stimulation, and then the currents of neurons were recorded by whole-cell patch clamp. The results showed that, under magnetic stimulation, the activation process of Na(+) channel was delayed, and the inactivation process was accelerated. Given the classic three-layer model, the polarization diagram of cell membrane potential distribution under pulse magnetic field was simulated, and it was found that the membrane potential induced was associated with the frequency and intensity of magnetic field. Also the effect of magnetic field-induced current on action potential was simulated by Hodgkin-Huxley (H-H) model. The result showed that the generation of action potential was delayed, and frequency and the amplitudes were decreased when working current was between -1.32 μA and 0 μA. When the working current was higher than 0 μA, the generation frequency of action potential was increased, and the change of amplitudes was not obvious, and when the working current was lower than -1.32 μA, the time of rising edge and amplitudes of action potential were decreased drastically, and the action potential was unable to generate. These results suggest that the magnetic field simulation can affect the distribution frequency and amplitude of action potential of neuron via sodium channel mediation.

Intracellular recording of action potentials by nanopillar electroporation.

PubMed

Xie, Chong; Lin, Ziliang; Hanson, Lindsey; Cui, Yi; Cui, Bianxiao

2012-02-12

Action potentials have a central role in the nervous system and in many cellular processes, notably those involving ion channels. The accurate measurement of action potentials requires efficient coupling between the cell membrane and the measuring electrodes. Intracellular recording methods such as patch clamping involve measuring the voltage or current across the cell membrane by accessing the cell interior with an electrode, allowing both the amplitude and shape of the action potentials to be recorded faithfully with high signal-to-noise ratios. However, the invasive nature of intracellular methods usually limits the recording time to a few hours, and their complexity makes it difficult to simultaneously record more than a few cells. Extracellular recording methods, such as multielectrode arrays and multitransistor arrays, are non-invasive and allow long-term and multiplexed measurements. However, extracellular recording sacrifices the one-to-one correspondence between the cells and electrodes, and also suffers from significantly reduced signal strength and quality. Extracellular techniques are not, therefore, able to record action potentials with the accuracy needed to explore the properties of ion channels. As a result, the pharmacological screening of ion-channel drugs is usually performed by low-throughput intracellular recording methods. The use of nanowire transistors, nanotube-coupled transistors and micro gold-spine and related electrodes can significantly improve the signal strength of recorded action potentials. Here, we show that vertical nanopillar electrodes can record both the extracellular and intracellular action potentials of cultured cardiomyocytes over a long period of time with excellent signal strength and quality. Moreover, it is possible to repeatedly switch between extracellular and intracellular recording by nanoscale electroporation and resealing processes. Furthermore, vertical nanopillar electrodes can detect subtle changes in action potentials induced by drugs that target ion channels.

Intracellular recording of action potentials by nanopillar electroporation

NASA Astrophysics Data System (ADS)

Xie, Chong; Lin, Ziliang; Hanson, Lindsey; Cui, Yi; Cui, Bianxiao

2012-03-01

Action potentials have a central role in the nervous system and in many cellular processes, notably those involving ion channels. The accurate measurement of action potentials requires efficient coupling between the cell membrane and the measuring electrodes. Intracellular recording methods such as patch clamping involve measuring the voltage or current across the cell membrane by accessing the cell interior with an electrode, allowing both the amplitude and shape of the action potentials to be recorded faithfully with high signal-to-noise ratios. However, the invasive nature of intracellular methods usually limits the recording time to a few hours, and their complexity makes it difficult to simultaneously record more than a few cells. Extracellular recording methods, such as multielectrode arrays and multitransistor arrays, are non-invasive and allow long-term and multiplexed measurements. However, extracellular recording sacrifices the one-to-one correspondence between the cells and electrodes, and also suffers from significantly reduced signal strength and quality. Extracellular techniques are not, therefore, able to record action potentials with the accuracy needed to explore the properties of ion channels. As a result, the pharmacological screening of ion-channel drugs is usually performed by low-throughput intracellular recording methods. The use of nanowire transistors, nanotube-coupled transistors and micro gold-spine and related electrodes can significantly improve the signal strength of recorded action potentials. Here, we show that vertical nanopillar electrodes can record both the extracellular and intracellular action potentials of cultured cardiomyocytes over a long period of time with excellent signal strength and quality. Moreover, it is possible to repeatedly switch between extracellular and intracellular recording by nanoscale electroporation and resealing processes. Furthermore, vertical nanopillar electrodes can detect subtle changes in action potentials induced by drugs that target ion channels.

Action potential bursts in central snail neurons elicited by paeonol: roles of ionic currents

PubMed Central

Chen, Yi-hung; Lin, Pei-lin; Hsu, Hui-yu; Wu, Ya-ting; Yang, Han-yin; Lu, Dah-yuu; Huang, Shiang-suo; Hsieh, Ching-liang; Lin, Jaung-geng

2010-01-01

Aim: To investigate the effects of 2′-hydroxy-4′-methoxyacetophenone (paeonol) on the electrophysiological behavior of a central neuron (right parietal 4; RP4) of the giant African snail (Achatina fulica Ferussac). Methods: Intracellular recordings and the two-electrode voltage clamp method were used to study the effects of paeonol on the RP4 neuron. Results: The RP4 neuron generated spontaneous action potentials. Bath application of paeonol at a concentration of ≥500 μmol/L reversibly elicited action potential bursts in a concentration-dependent manner. Immersing the neurons in Co2+-substituted Ca2+-free solution did not block paeonol-elicited bursting. Pretreatment with the protein kinase A (PKA) inhibitor KT-5720 or the protein kinase C (PKC) inhibitor Ro 31-8220 did not affect the action potential bursts. Voltage-clamp studies revealed that paeonol at a concentration of 500 μmol/L had no remarkable effects on the total inward currents, whereas paeonol decreased the delayed rectifying K+ current (IKD) and the fast-inactivating K+ current (IA). Application of 4-aminopyridine (4-AP 5 mmol/L), an inhibitor of IA, or charybdotoxin 250 nmol/L, an inhibitor of the Ca2+-activated K+ current (IK(Ca)), failed to elicit action potential bursts, whereas tetraethylammonium chloride (TEA 50 mmol/L), an IKD blocker, successfully elicited action potential bursts. At a lower concentration of 5 mmol/L, TEA facilitated the induction of action potential bursts elicited by paeonol. Conclusion: Paeonol elicited a bursting firing pattern of action potentials in the RP4 neuron and this activity relates closely to the inhibitory effects of paeonol on the IKD. PMID:21042287

Consequences of converting graded to action potentials upon neural information coding and energy efficiency.

PubMed

Sengupta, Biswa; Laughlin, Simon Barry; Niven, Jeremy Edward

2014-01-01

Information is encoded in neural circuits using both graded and action potentials, converting between them within single neurons and successive processing layers. This conversion is accompanied by information loss and a drop in energy efficiency. We investigate the biophysical causes of this loss of information and efficiency by comparing spiking neuron models, containing stochastic voltage-gated Na(+) and K(+) channels, with generator potential and graded potential models lacking voltage-gated Na(+) channels. We identify three causes of information loss in the generator potential that are the by-product of action potential generation: (1) the voltage-gated Na(+) channels necessary for action potential generation increase intrinsic noise and (2) introduce non-linearities, and (3) the finite duration of the action potential creates a 'footprint' in the generator potential that obscures incoming signals. These three processes reduce information rates by ∼50% in generator potentials, to ∼3 times that of spike trains. Both generator potentials and graded potentials consume almost an order of magnitude less energy per second than spike trains. Because of the lower information rates of generator potentials they are substantially less energy efficient than graded potentials. However, both are an order of magnitude more efficient than spike trains due to the higher energy costs and low information content of spikes, emphasizing that there is a two-fold cost of converting analogue to digital; information loss and cost inflation.

Consequences of Converting Graded to Action Potentials upon Neural Information Coding and Energy Efficiency

PubMed Central

Sengupta, Biswa; Laughlin, Simon Barry; Niven, Jeremy Edward

2014-01-01

Information is encoded in neural circuits using both graded and action potentials, converting between them within single neurons and successive processing layers. This conversion is accompanied by information loss and a drop in energy efficiency. We investigate the biophysical causes of this loss of information and efficiency by comparing spiking neuron models, containing stochastic voltage-gated Na+ and K+ channels, with generator potential and graded potential models lacking voltage-gated Na+ channels. We identify three causes of information loss in the generator potential that are the by-product of action potential generation: (1) the voltage-gated Na+ channels necessary for action potential generation increase intrinsic noise and (2) introduce non-linearities, and (3) the finite duration of the action potential creates a ‘footprint’ in the generator potential that obscures incoming signals. These three processes reduce information rates by ∼50% in generator potentials, to ∼3 times that of spike trains. Both generator potentials and graded potentials consume almost an order of magnitude less energy per second than spike trains. Because of the lower information rates of generator potentials they are substantially less energy efficient than graded potentials. However, both are an order of magnitude more efficient than spike trains due to the higher energy costs and low information content of spikes, emphasizing that there is a two-fold cost of converting analogue to digital; information loss and cost inflation. PMID:24465197

Synchronization of action potentials during low-magnesium-induced bursting

PubMed Central

Johnson, Sarah E.; Hudson, John L.

2015-01-01

The relationship between mono- and polysynaptic strength and action potential synchronization was explored using a reduced external Mg2+ model. Single and dual whole cell patch-clamp recordings were performed in hippocampal cultures in three concentrations of external Mg2+. In decreased Mg2+ medium, the individual cells transitioned to spontaneous bursting behavior. In lowered Mg2+ media the larger excitatory synaptic events were observed more frequently and fewer transmission failures occurred, suggesting strengthened synaptic transmission. The event synchronization was calculated for the neural action potentials of the cell pairs, and it increased in media where Mg2+ concentration was lowered. Analysis of surrogate data where bursting was present, but no direct or indirect connections existed between the neurons, showed minimal action potential synchronization. This suggests the synchronization of action potentials is a product of the strengthening synaptic connections within neuronal networks. PMID:25609103

Synchronization of action potentials during low-magnesium-induced bursting.

PubMed

Johnson, Sarah E; Hudson, John L; Kapur, Jaideep

2015-04-01

The relationship between mono- and polysynaptic strength and action potential synchronization was explored using a reduced external Mg(2+) model. Single and dual whole cell patch-clamp recordings were performed in hippocampal cultures in three concentrations of external Mg(2+). In decreased Mg(2+) medium, the individual cells transitioned to spontaneous bursting behavior. In lowered Mg(2+) media the larger excitatory synaptic events were observed more frequently and fewer transmission failures occurred, suggesting strengthened synaptic transmission. The event synchronization was calculated for the neural action potentials of the cell pairs, and it increased in media where Mg(2+) concentration was lowered. Analysis of surrogate data where bursting was present, but no direct or indirect connections existed between the neurons, showed minimal action potential synchronization. This suggests the synchronization of action potentials is a product of the strengthening synaptic connections within neuronal networks. Copyright © 2015 the American Physiological Society.

Millisecond infrared laser pulses depolarize and elicit action potentials on in-vitro dorsal root ganglion neurons

PubMed Central

Paris, Lambert; Marc, Isabelle; Charlot, Benoit; Dumas, Michel; Valmier, Jean; Bardin, Fabrice

2017-01-01

This work focuses on the optical stimulation of dorsal root ganglion (DRG) neurons through infrared laser light stimulation. We show that a few millisecond laser pulse at 1875 nm induces a membrane depolarization, which was observed by the patch-clamp technique. This stimulation led to action potentials firing on a minority of neurons beyond an energy threshold. A depolarization without action potential was observed for the majority of DRG neurons, even beyond the action potential energy threshold. The use of ruthenium red, a thermal channel blocker, stops the action potential generation, but has no effects on membrane depolarization. Local temperature measurements reveal that the depolarization amplitude is sensitive to the amplitude of the temperature rise as well as to the time rate of change of temperature, but in a way which may not fully follow a photothermal capacitive mechanism, suggesting that more complex mechanisms are involved. PMID:29082085

[Effects of dauricine on action potentials and slow inward currents of guinea pig ventricular papillary muscles].

PubMed

Li, S N; Zhang, K Y

1992-11-01

Effects of dauricine (Dau) on the action potentials (AP), the slow action potentials (SAP), and the slow inward currents (Isi) of guinea pig ventricular papillary muscles were observed by means of intracellular microelectrode and single sucrose gap voltage clamp technique. In the early stage, Dau shortened action potential duration 100 (APD100) and effective refractory period (ERP) (ERP/APD < 1; P < 0.01), but did not affect APD20 and other parameters. In the late stage, Dau prolonged APD100, ERP, and APD20, significantly decreased action potential amplitude (APA), maximum velocity (Vmax), and overshot (OS) (ERP/APD > 1; P < 0.01), greatly diminished APA and OS of SAP induced by isoprenaline (P < 0.01), and remarkably inhibited Isi (P < 0.01). The results suggested that Dau exerted an inhibitory effect on Na+, Ca2+, and K+ channels.

Simulation of axonal excitability using a Spreadsheet template created in Microsoft Excel.

PubMed

Brown, A M

2000-08-01

The objective of this present study was to implement an established simulation protocol (A.M. Brown, A methodology for simulating biological systems using Microsoft Excel, Comp. Methods Prog. Biomed. 58 (1999) 181-90) to model axonal excitability. The simulation protocol involves the use of in-cell formulas directly typed into a spreadsheet and does not require any programming skills or use of the macro language. Once the initial spreadsheet template has been set up the simulations described in this paper can be executed with a few simple keystrokes. The model axon contained voltage-gated ion channels that were modeled using Hodgkin Huxley style kinetics. The basic properties of axonal excitability modeled were: (1) threshold of action potential firing, demonstrating that not only are the stimulus amplitude and duration critical in the generation of an action potential, but also the resting membrane potential; (2) refractoriness, the phenomenon of reduced excitability immediately following an action potential. The difference between the absolute refractory period, when no amount of stimulus will elicit an action potential, and relative refractory period, when an action potential may be generated by applying increased stimulus, was demonstrated with regard to the underlying state of the Na(+) and K(+) channels; (3) temporal summation, a process by which two sub-threshold stimuli can unite to elicit an action potential was shown to be due to conductance changes outlasting the first stimulus and summing with the second stimulus-induced conductance changes to drive the membrane potential past threshold; (4) anode break excitation, where membrane hyperpolarization was shown to produce an action potential by removing Na(+) channel inactivation that is present at resting membrane potential. The simulations described in this paper provide insights into mechanisms of axonal excitation that can be carried out by following an easily understood protocol.

Optical mapping of optogenetically shaped cardiac action potentials.

PubMed

Park, Sarah A; Lee, Shin-Rong; Tung, Leslie; Yue, David T

2014-08-19

Light-mediated silencing and stimulation of cardiac excitability, an important complement to electrical stimulation, promises important discoveries and therapies. To date, cardiac optogenetics has been studied with patch-clamp, multielectrode arrays, video microscopy, and an all-optical system measuring calcium transients. The future lies in achieving simultaneous optical acquisition of excitability signals and optogenetic control, both with high spatio-temporal resolution. Here, we make progress by combining optical mapping of action potentials with concurrent activation of channelrhodopsin-2 (ChR2) or halorhodopsin (eNpHR3.0), via an all-optical system applied to monolayers of neonatal rat ventricular myocytes (NRVM). Additionally, we explore the capability of ChR2 and eNpHR3.0 to shape action-potential waveforms, potentially aiding the study of short/long QT syndromes that result from abnormal changes in action potential duration (APD). These results show the promise of an all-optical system to acquire action potentials with precise temporal optogenetics control, achieving a long-sought flexibility beyond the means of conventional electrical stimulation.

Optical mapping of optogenetically shaped cardiac action potentials

PubMed Central

Park, Sarah A.; Lee, Shin-Rong; Tung, Leslie; Yue, David T.

2014-01-01

Light-mediated silencing and stimulation of cardiac excitability, an important complement to electrical stimulation, promises important discoveries and therapies. To date, cardiac optogenetics has been studied with patch-clamp, multielectrode arrays, video microscopy, and an all-optical system measuring calcium transients. The future lies in achieving simultaneous optical acquisition of excitability signals and optogenetic control, both with high spatio-temporal resolution. Here, we make progress by combining optical mapping of action potentials with concurrent activation of channelrhodopsin-2 (ChR2) or halorhodopsin (eNpHR3.0), via an all-optical system applied to monolayers of neonatal rat ventricular myocytes (NRVM). Additionally, we explore the capability of ChR2 and eNpHR3.0 to shape action-potential waveforms, potentially aiding the study of short/long QT syndromes that result from abnormal changes in action potential duration (APD). These results show the promise of an all-optical system to acquire action potentials with precise temporal optogenetics control, achieving a long-sought flexibility beyond the means of conventional electrical stimulation. PMID:25135113

Injury risk associated with playing actions during competitive soccer

PubMed Central

Rahnama, N; Reilly, T; Lees, A

2002-01-01

Objective: To assess the exposure of players to injury risk during English Premier League soccer matches in relation to selected factors. Methods: Injury risk was assessed by rating the injury potential of playing actions during competition with respect to (a) type of playing action, (b) period of the game, (c) zone of the pitch, and (d) playing either at home or away. In all, 10 games from the English Premier League 1999–2000 were chosen for analysis. A notation system was used whereby 16 soccer specific playing actions were classified into three categories: those inducing actual injury, those with a potential for injury (graded as mild, moderate, or high), and those deemed to have no potential for injury. The pitch was divided into 18 zones, and the position of each event was recorded along with time elapsed in the game, enabling six 15 minute periods to be defined. Results: Close to 18 000 actions were notated. On average (mean (SD)), 1788 (73) events (one every three seconds), 767 (99) events with injury potential (one every six seconds), and 2 (1) injuries (one every 45 minutes) per game were recorded. An overall injury incidence of 53 per 1000 playing hours was calculated. Receiving a tackle, receiving a "charge", and making a tackle were categorised as having a substantial injury risk, and goal catch, goal punch, kicking the ball, shot on goal, set kick, and heading the ball were all categorised as having a significant injury risk. All other actions were deemed low in risk. The first 15 minutes of each half contained the highest number of actions with mild injury potential, the last 15 minutes having the highest number of actions with moderate injury potential (p<0.01). The first and last 15 minutes of the game had the highest number of actions with high injury potential, although not significant. More actions with mild injury potential occurred in the goal area, and more actions with moderate and high injury potential occurred in the zone adjacent to the goal area (p<0.001). There was no significant difference between home and away with regard to injury potential. Conclusions: Playing actions with high injury risk were linked to contesting possession. Injury risk was highest in the first and last 15 minutes of the game, reflecting the intense engagements in the opening period and the possible effect of fatigue in the closing period. Injury risk was concentrated in the areas of the pitch where possession of the ball is most vigorously contested, which were specific attacking and defending zones close to the goal. Injury potential was no greater in away matches than at home. PMID:12351333

Spontaneous action potentials and neural coding in unmyelinated axons.

PubMed

O'Donnell, Cian; van Rossum, Mark C W

2015-04-01

The voltage-gated Na and K channels in neurons are responsible for action potential generation. Because ion channels open and close in a stochastic fashion, spontaneous (ectopic) action potentials can result even in the absence of stimulation. While spontaneous action potentials have been studied in detail in single-compartment models, studies on spatially extended processes have been limited. The simulations and analysis presented here show that spontaneous rate in unmyelinated axon depends nonmonotonically on the length of the axon, that the spontaneous activity has sub-Poisson statistics, and that neural coding can be hampered by the spontaneous spikes by reducing the probability of transmitting the first spike in a train.

Improving Cardiac Action Potential Measurements: 2D and 3D Cell Culture.

PubMed

Daily, Neil J; Yin, Yue; Kemanli, Pinar; Ip, Brian; Wakatsuki, Tetsuro

2015-11-01

Progress in the development of assays for measuring cardiac action potential is crucial for the discovery of drugs for treating cardiac disease and assessing cardiotoxicity. Recently, high-throughput methods for assessing action potential using induced pluripotent stem cell (iPSC) derived cardiomyocytes in both two-dimensional monolayer cultures and three-dimensional tissues have been developed. We describe an improved method for assessing cardiac action potential using an ultra-fast cost-effective plate reader with commercially available dyes. Our methods improve dramatically the detection of the fluorescence signal from these dyes and make way for the development of more high-throughput methods for cardiac drug discovery and cardiotoxicity.

Action potentials contribute to epileptic high-frequency oscillations recorded with electrodes remote from neurons.

PubMed

Kobayashi, Katsuhiro; Akiyama, Tomoyuki; Ohmori, Iori; Yoshinaga, Harumi; Gotman, Jean

2015-05-01

The importance of epileptic high-frequency oscillations (HFOs) in electroencephalogram (EEG) is growing. Action potentials generating some HFOs are observed in the vicinity of neurons in experimental animals. However electrodes that are remote from neurons, as in case of clinical situations, should not record action potentials. We propose to resolve this question by a realistic simulation of epileptic neuronal network. The rat dentate gyrus with sclerosis was simulated in silico. We computed the current dipole moment generated by each granule cell and the field potentials in a measurement area far from neurons. The dentate gyrus was stimulated through synaptic input to evoke discharges resembling interictal epileptiform discharges, which had superimposed HFOs⩽295Hz that were recordable with remote electrodes and represented bursts of action potentials of granule cells. The increase in power of HFOs was associated with the progression of sclerosis, the reduction of GABAergic inhibition, and the increase in cell connectivity. Spectral frequency of HFOs had similar tendencies. HFOs recorded with electrodes remote from neurons could actually be generated by clusters of action potentials. The phenomenon of action potentials recorded with remote electrodes can possibly extend the clinical meaning of EEG. Copyright © 2014 International Federation of Clinical Neurophysiology. Published by Elsevier Ireland Ltd. All rights reserved.

A physical action potential generator: design, implementation and evaluation.

PubMed

Latorre, Malcolm A; Chan, Adrian D C; Wårdell, Karin

2015-01-01

The objective was to develop a physical action potential generator (Paxon) with the ability to generate a stable, repeatable, programmable, and physiological-like action potential. The Paxon has an equivalent of 40 nodes of Ranvier that were mimicked using resin embedded gold wires (Ø = 20 μm). These nodes were software controlled and the action potentials were initiated by a start trigger. Clinically used Ag-AgCl electrodes were coupled to the Paxon for functional testing. The Paxon's action potential parameters were tunable using a second order mathematical equation to generate physiologically relevant output, which was accomplished by varying the number of nodes involved (1-40 in incremental steps of 1) and the node drive potential (0-2.8 V in 0.7 mV steps), while keeping a fixed inter-nodal timing and test electrode configuration. A system noise floor of 0.07 ± 0.01 μV was calculated over 50 runs. A differential test electrode recorded a peak positive amplitude of 1.5 ± 0.05 mV (gain of 40x) at time 196.4 ± 0.06 ms, including a post trigger delay. The Paxon's programmable action potential like signal has the possibility to be used as a validation test platform for medical surface electrodes and their attached systems.

Direct detection of a single evoked action potential with MRS in Lumbricus terrestris.

PubMed

Poplawsky, Alexander J; Dingledine, Raymond; Hu, Xiaoping P

2012-01-01

Functional MRI (fMRI) measures neural activity indirectly by detecting the signal change associated with the hemodynamic response following brain activation. In order to alleviate the temporal and spatial specificity problems associated with fMRI, a number of attempts have been made to detect neural magnetic fields (NMFs) with MRI directly, but have thus far provided conflicting results. In this study, we used MR to detect axonal NMFs in the median giant fiber of the earthworm, Lumbricus terrestris, by examining the free induction decay (FID) with a sampling interval of 0.32 ms. The earthworm nerve cords were isolated from the vasculature and stimulated at the threshold of action potential generation. FIDs were acquired shortly after the stimulation, and simultaneous field potential recordings identified the presence or absence of single evoked action potentials. FIDs acquired when the stimulus did not evoke an action potential were summed as background. The phase of the background-subtracted FID exhibited a systematic change, with a peak phase difference of (-1.2 ± 0.3) × 10(-5) radians occurring at a time corresponding to the timing of the action potential. In addition, we calculated the possible changes in the FID magnitude and phase caused by a simulated action potential using a volume conductor model. The measured phase difference matched the theoretical prediction well in both amplitude and temporal characteristics. This study provides the first evidence for the direct detection of a magnetic field from an evoked action potential using MR. Copyright © 2011 John Wiley & Sons, Ltd.

The Direct Detection of a Single Evoked Action Potential with Magnetic Resonance Spectroscopy in Lumbricus Terrestris

PubMed Central

Poplawsky, Alexander J.; Dingledine, Raymond

2011-01-01

Functional MRI (fMRI) indirectly measures neural activity by detecting the signal change associated with the hemodynamic response following brain activation. In order to alleviate the temporal and spatial specificity problems associated with fMRI, a number of attempts have been made to detect neural magnetic fields (NMFs) with MRI directly, but have thus far provided conflicting results. In the present study, we used magnetic resonance to detect axonal NMFs in the median giant fiber of the earthworm, Lumbricus terrestris, by examining the free-induction decay (FID) with a sampling interval of 0.32 ms. The earthworm nerve cords were isolated from the vasculature and stimulated at the threshold of action potential generation. FIDs were acquired shortly after the stimulation and simultaneous field potential recordings identified the presence or absence of single evoked action potentials. FIDs acquired when the stimulus did not evoke an action potential were summed as background. The phase of the background-subtracted FID exhibited a systematic change, with a peak phase difference of [-1.2 ± 0.3] ×10-5 radians occurring at a time corresponding to the timing of the action potential. In addition, we calculated the possible changes in the FID magnitude and phase due to a simulated action potential using a volume conductor model. The measured phase difference matched the theoretical prediction well in both amplitude and temporal characteristics. This study provides the first evidence for the direct detection of a magnetic field from an evoked action potential using magnetic resonance. PMID:21728204

Channel sialic acids limit hERG channel activity during the ventricular action potential.

PubMed

Norring, Sarah A; Ednie, Andrew R; Schwetz, Tara A; Du, Dongping; Yang, Hui; Bennett, Eric S

2013-02-01

Activity of human ether-a-go-go-related gene (hERG) 1 voltage-gated K(+) channels is responsible for portions of phase 2 and phase 3 repolarization of the human ventricular action potential. Here, we questioned whether and how physiologically and pathophysiologically relevant changes in surface N-glycosylation modified hERG channel function. Voltage-dependent hERG channel gating and activity were evaluated as expressed in a set of Chinese hamster ovary (CHO) cell lines under conditions of full glycosylation, no sialylation, no complex N-glycans, and following enzymatic deglycosylation of surface N-glycans. For each condition of reduced glycosylation, hERG channel steady-state activation and inactivation relationships were shifted linearly by significant depolarizing ∼9 and ∼18 mV, respectively. The hERG window current increased significantly by 50-150%, and the peak shifted by a depolarizing ∼10 mV. There was no significant change in maximum hERG current density. Deglycosylated channels were significantly more active (20-80%) than glycosylated controls during phases 2 and 3 of action potential clamp protocols. Simulations of hERG current and ventricular action potentials corroborated experimental data and predicted reduced sialylation leads to a 50-70-ms decrease in action potential duration. The data describe a novel mechanism by which hERG channel gating is modulated through physiologically and pathophysiologically relevant changes in N-glycosylation; reduced channel sialylation increases hERG channel activity during the action potential, thereby increasing the rate of action potential repolarization.

Sodium and calcium currents shape action potentials in immature mouse inner hair cells

PubMed Central

Marcotti, Walter; Johnson, Stuart L; Rüsch, Alfons; Kros, Corné J

2003-01-01

Before the onset of hearing at postnatal day 12, mouse inner hair cells (IHCs) produce spontaneous and evoked action potentials. These spikes are likely to induce neurotransmitter release onto auditory nerve fibres. Since immature IHCs express both α1D (Cav1.3) Ca2+ and Na+ currents that activate near the resting potential, we examined whether these two conductances are involved in shaping the action potentials. Both had extremely rapid activation kinetics, followed by fast and complete voltage-dependent inactivation for the Na+ current, and slower, partially Ca2+-dependent inactivation for the Ca2+ current. Only the Ca2+ current is necessary for spontaneous and induced action potentials, and 29 % of cells lacked a Na+ current. The Na+ current does, however, shorten the time to reach the action-potential threshold, whereas the Ca2+ current is mainly involved, together with the K+ currents, in determining the speed and size of the spikes. Both currents increased in size up to the end of the first postnatal week. After this, the Ca2+ current reduced to about 30 % of its maximum size and persisted in mature IHCs. The Na+ current was downregulated around the onset of hearing, when the spiking is also known to disappear. Although the Na+ current was observed as early as embryonic day 16.5, its role in action-potential generation was only evident from just after birth, when the resting membrane potential became sufficiently negative to remove a sizeable fraction of the inactivation (half inactivation was at −71 mV). The size of both currents was positively correlated with the developmental change in action-potential frequency. PMID:12937295

The dependence of the action potential of the frog's heart on the external and intracellular sodium concentration

PubMed Central

Niedergerke, R.; Orkand, R. K.

1966-01-01

1. The overshoot of the action potential of the frog's heart was reduced when external sodium chloride was replaced by sucrose. However, the potential decrement was only 17·3 mV for a 10-fold reduction of sodium as compared with 58 mV expected on the basis of the sodium hypothesis of excitation. 2. Replacement of up to 75% of the external sodium by choline did not reduce the overshoot, provided atropine was present in sufficient concentrations to suppress any parasympathomimetic action. 3. The maximum rate of rise of the action potential markedly declined in low sodium fluids whether sucrose or choline chloride was used to replace sodium chloride. 4. The maximum rate of rise was reduced to only a small extent when external sodium was replaced by lithium. 5. Increasing the intracellular sodium concentration in exchange for lost potassium caused overshoots to decline. The effects resembled those obtained in similar experiments with skeletal muscle fibres (Desmedt, 1953). 6. Action potentials occurring under certain conditions even in the presence of very low external sodium concentrations (≤ 5% normal) also declined in height when the intracellular sodium concentration was increased. 7. The behaviour of the action potential in low external sodium concentrations may be explained by an action of calcium on the excitable membrane. PMID:5921833

Rapid Ca2+ flux through the transverse tubular membrane, activated by individual action potentials in mammalian skeletal muscle

PubMed Central

Launikonis, Bradley S; Stephenson, D George; Friedrich, Oliver

2009-01-01

Periods of low frequency stimulation are known to increase the net Ca2+ uptake in skeletal muscle but the mechanism responsible for this Ca2+ entry is not known. In this study a novel high-resolution fluorescence microscopy approach allowed the detection of an action potential-induced Ca2+ flux across the tubular (t-) system of rat extensor digitorum longus muscle fibres that appears to be responsible for the net uptake of Ca2+ in working muscle. Action potentials were triggered in the t-system of mechanically skinned fibres from rat by brief field stimulation and t-system [Ca2+] ([Ca2+]t-sys) and cytoplasmic [Ca2+] ([Ca2+]cyto) were simultaneously resolved on a confocal microscope. When initial [Ca2+]t-sys was ≥ 0.2 mm a Ca2+ flux from t-system to the cytoplasm was observed following a single action potential. The action potential-induced Ca2+ flux and associated t-system Ca2+ permeability decayed exponentially and displayed inactivation characteristics such that further Ca2+ entry across the t-system could not be observed after 2–3 action potentials at 10 Hz stimulation rate. When [Ca2+]t-sys was closer to 0.1 mm, a transient rise in [Ca2+]t-sys was observed almost concurrently with the increase in [Ca2+]cyto following the action potential. The change in direction of Ca2+ flux was consistent with changes in the direction of the driving force for Ca2+. This is the first demonstration of a rapid t-system Ca2+ flux associated with a single action potential in mammalian skeletal muscle. The properties of this channel are inconsistent with a flux through the L-type Ca2+ channel suggesting that an as yet unidentified t-system protein is conducting this current. This action potential-activated Ca2+ flux provides an explanation for the previously described Ca2+ entry and accumulation observed with prolonged, intermittent muscle activity. PMID:19332499

29 CFR 1990.147 - Final action.

Code of Federal Regulations, 2014 CFR

2014-07-01

...) IDENTIFICATION, CLASSIFICATION, AND REGULATION OF POTENTIAL OCCUPATIONAL CARCINOGENS Regulation of Potential Occupational Carcinogens § 1990.147 Final action. (a) Within one hundred twenty (120) days from the last day of... is classified as a Category I Potential Carcinogen or as a Category II Potential Carcinogen. If the...

29 CFR 1990.147 - Final action.

Code of Federal Regulations, 2012 CFR

2012-07-01

...) IDENTIFICATION, CLASSIFICATION, AND REGULATION OF POTENTIAL OCCUPATIONAL CARCINOGENS Regulation of Potential Occupational Carcinogens § 1990.147 Final action. (a) Within one hundred twenty (120) days from the last day of... is classified as a Category I Potential Carcinogen or as a Category II Potential Carcinogen. If the...

29 CFR 1990.147 - Final action.

Code of Federal Regulations, 2013 CFR

2013-07-01

...) IDENTIFICATION, CLASSIFICATION, AND REGULATION OF POTENTIAL OCCUPATIONAL CARCINOGENS Regulation of Potential Occupational Carcinogens § 1990.147 Final action. (a) Within one hundred twenty (120) days from the last day of... is classified as a Category I Potential Carcinogen or as a Category II Potential Carcinogen. If the...

29 CFR 1990.147 - Final action.

Code of Federal Regulations, 2011 CFR

2011-07-01

...) IDENTIFICATION, CLASSIFICATION, AND REGULATION OF POTENTIAL OCCUPATIONAL CARCINOGENS Regulation of Potential Occupational Carcinogens § 1990.147 Final action. (a) Within one hundred twenty (120) days from the last day of... is classified as a Category I Potential Carcinogen or as a Category II Potential Carcinogen. If the...

Effect of Exogenous Extracellular Nicotinamide Adenine Dinucleotide (NAD⁺) on Bioelectric Activity of the Pacemaker and Conduction System of the Heart.

PubMed

Pustovit, K B; Kuz'min, V S; Sukhova, G S

2015-06-01

In rat sinoatrial node, NAD(+) (10 μM) reduced the rate of spontaneous action potentials, duration of action potentials, and the velocity of slow diastolic depolarization, but the rate of action potential front propagation increases. In passed rabbit Purkinje fibers, NAD(+) (10 μM) reduced the duration of action potentials. Under conditions of spontaneous activity of Purkinje fibers, NAD(+) reduced the fi ring rate and the rate of slow diastolic depolarization. The effects of extracellular NAD(+) on bioelectric activity of the pacemaker (sinoatrial node) and conduction system of the heart (Purkinje fibers) are probably related to activation of P1 and P2 purinoceptors.

Rapid time course of action potentials in spines and remote dendrites of mouse visual cortex neurons.

PubMed

Holthoff, Knut; Zecevic, Dejan; Konnerth, Arthur

2010-04-01

Axonally initiated action potentials back-propagate into spiny dendrites of central mammalian neurons and thereby regulate plasticity at excitatory synapses on individual spines as well as linear and supralinear integration of synaptic inputs along dendritic branches. Thus, the electrical behaviour of individual dendritic spines and terminal dendritic branches is critical for the integrative function of nerve cells. The actual dynamics of action potentials in spines and terminal branches, however, are not entirely clear, mostly because electrode recording from such small structures is not feasible. Additionally, the available membrane potential imaging techniques are limited in their sensitivity and require substantial signal averaging for the detection of electrical events at the spatial scale of individual spines. We made a critical improvement in the voltage-sensitive dye imaging technique to achieve multisite recordings of backpropagating action potentials from individual dendritic spines at a high frame rate. With this approach, we obtained direct evidence that in layer 5 pyramidal neurons from the visual cortex of juvenile mice, the rapid time course of somatic action potentials is preserved throughout all cellular compartments, including dendritic spines and terminal branches of basal and apical dendrites. The rapid time course of the action potential in spines may be a critical determinant for the precise regulation of spike timing-dependent synaptic plasticity within a narrow time window.

22 CFR 161.8 - General description of the Department's NEPA process.

Code of Federal Regulations, 2010 CFR

2010-04-01

... § 161.8 General description of the Department's NEPA process. In reviewing proposed actions for potential environmental effects in the United States responsible action officers will follow the procedural... review the action to determine if it may cause potential significant environmental effects on the...

Prolonged action potential duration in cardiac ablation of PDK1 mice.

PubMed

Han, Zhonglin; Jiang, Yu; Yang, Zhongzhou; Cao, Kejiang; Wang, Dao W

2015-01-01

The involvement of the AGC protein kinase family in regulating arrhythmia has drawn considerable attention, but the underlying mechanisms are still not clear. The aim of this study is to explore the role of 3-phosphoinositide-dependent protein kinase-1 (PDK1), one of upstream protein kinases of the AGC protein kinase family, in the pathogenesis of dysregulated electrophysiological basis. PDK1(F/F) αMHC-Cre mice and PDK1(F/F) mice were divided into experiment group and control group. Using patch clamping technology, we explored action potential duration in both groups, and investigated the functions of transient outward potassium channel and L-type Ca(2+) channel to explain the abnormal action potential duration. Significant prolongation action potential duration was found in mice with PDK1 deletion. Further, the peak current of transient outward potassium current and L-type Ca(2+) current were decreased by 84% and 49% respectively. In addition, dysregulation of channel kinetics lead to action potential duration prolongation further. In conclusion, we have demonstrated that PDK1 participates in action potential prolongation in cardiac ablation of PDK1 mice. This effect is likely to be mediated largely through downregulation of transient outward potassium current. These findings indicate the modulation of the PDK1 pathway could provide a new mechanism for abnormal electrophysiological basis.

Back-Propagation of Physiological Action Potential Output in Dendrites of Slender-Tufted L5A Pyramidal Neurons

PubMed Central

Grewe, Benjamin F.; Bonnan, Audrey; Frick, Andreas

2009-01-01

Pyramidal neurons of layer 5A are a major neocortical output type and clearly distinguished from layer 5B pyramidal neurons with respect to morphology, in vivo firing patterns, and connectivity; yet knowledge of their dendritic properties is scant. We used a combination of whole-cell recordings and Ca2+ imaging techniques in vitro to explore the specific dendritic signaling role of physiological action potential patterns recorded in vivo in layer 5A pyramidal neurons of the whisker-related ‘barrel cortex’. Our data provide evidence that the temporal structure of physiological action potential patterns is crucial for an effective invasion of the main apical dendrites up to the major branch point. Both the critical frequency enabling action potential trains to invade efficiently and the dendritic calcium profile changed during postnatal development. In contrast to the main apical dendrite, the more passive properties of the short basal and apical tuft dendrites prevented an efficient back-propagation. Various Ca2+ channel types contributed to the enhanced calcium signals during high-frequency firing activity, whereas A-type K+ and BKCa channels strongly suppressed it. Our data support models in which the interaction of synaptic input with action potential output is a function of the timing, rate and pattern of action potentials, and dendritic location. PMID:20508744

A phantom axon setup for validating models of action potential recordings.

PubMed

Rossel, Olivier; Soulier, Fabien; Bernard, Serge; Guiraud, David; Cathébras, Guy

2016-08-01

Electrode designs and strategies for electroneurogram recordings are often tested first by computer simulations and then by animal models, but they are rarely implanted for long-term evaluation in humans. The models show that the amplitude of the potential at the surface of an axon is higher in front of the nodes of Ranvier than at the internodes; however, this has not been investigated through in vivo measurements. An original experimental method is presented to emulate a single fiber action potential in an infinite conductive volume, allowing the potential of an axon to be recorded at both the nodes of Ranvier and the internodes, for a wide range of electrode-to-fiber radial distances. The paper particularly investigates the differences in the action potential amplitude along the longitudinal axis of an axon. At a short radial distance, the action potential amplitude measured in front of a node of Ranvier is two times larger than in the middle of two nodes. Moreover, farther from the phantom axon, the measured action potential amplitude is almost constant along the longitudinal axis. The results of this new method confirm the computer simulations, with a correlation of 97.6 %.

Action potentials in retinal ganglion cells are initiated at the site of maximal curvature of the extracellular potential.

PubMed

Eickenscheidt, Max; Zeck, Günther

2014-06-01

The initiation of an action potential by extracellular stimulation occurs after local depolarization of the neuronal membrane above threshold. Although the technique shows remarkable clinical success, the site of action and the relevant stimulation parameters are not completely understood. Here we identify the site of action potential initiation in rabbit retinal ganglion cells (RGCs) interfaced to an array of extracellular capacitive stimulation electrodes. We determine which feature of the extracellular potential governs action potential initiation by simultaneous stimulation and recording RGCs interfaced in epiretinal configuration. Stimulation electrodes were combined to areas of different size and were presented at different positions with respect to the RGC. Based on stimulation by electrodes beneath the RGC soma and simultaneous sub-millisecond latency measurement we infer axonal initiation at the site of maximal curvature of the extracellular potential. Stimulation by electrodes at different positions along the axon reveals a nearly constant threshold current density except for a narrow region close to the cell soma. These findings are explained by the concept of the activating function modified to consider a region of lower excitability close to the cell soma. We present a framework how to estimate the site of action potential initiation and the stimulus required to cross threshold in neurons tightly interfaced to capacitive stimulation electrodes. Our results underscore the necessity of rigorous electrical characterization of the stimulation electrodes and of the interfaced neural tissue.

Autonomous initiation and propagation of action potentials in neurons of the subthalamic nucleus.

PubMed

Atherton, Jeremy F; Wokosin, David L; Ramanathan, Sankari; Bevan, Mark D

2008-12-01

The activity of the subthalamic nucleus (STN) is intimately related to movement and is generated, in part, by voltage-dependent Na(+) (Na(v)) channels that drive autonomous firing. In order to determine the principles underlying the initiation and propagation of action potentials in STN neurons, 2-photon laser scanning microscopy was used to guide tight-seal whole-cell somatic and loose-seal cell-attached axonal/dendritic patch-clamp recordings and compartment-selective ion channel manipulation in rat brain slices. Action potentials were first detected in a region that corresponded most closely to the unmyelinated axon initial segment, as defined by Golgi and ankyrin G labelling. Following initiation, action potentials propagated reliably into axonal and somatodendritic compartments with conduction velocities of approximately 5 m s(-1) and approximately 0.7 m s(-1), respectively. Action potentials generated by neurons with axons truncated within or beyond the axon initial segment were not significantly different. However, axon initial segment and somatic but not dendritic or more distal axonal application of low [Na(+)] ACSF or the selective Na(v) channel blocker tetrodotoxin consistently depolarized action potential threshold. Finally, somatodendritic but not axonal application of GABA evoked large, rapid inhibitory currents in concordance with electron microscopic analyses, which revealed that the somatodendritic compartment was the principal target of putative inhibitory inputs. Together the data are consistent with the conclusions that in STN neurons the axon initial segment and soma express an excess of Na(v) channels for the generation of autonomous activity, while synaptic activation of somatodendritic GABA(A) receptors regulates the axonal initiation of action potentials.

Autonomous initiation and propagation of action potentials in neurons of the subthalamic nucleus

PubMed Central

Atherton, Jeremy F; Wokosin, David L; Ramanathan, Sankari; Bevan, Mark D

2008-01-01

The activity of the subthalamic nucleus (STN) is intimately related to movement and is generated, in part, by voltage-dependent Na+ (Nav) channels that drive autonomous firing. In order to determine the principles underlying the initiation and propagation of action potentials in STN neurons, 2-photon laser scanning microscopy was used to guide tight-seal whole-cell somatic and loose-seal cell-attached axonal/dendritic patch-clamp recordings and compartment-selective ion channel manipulation in rat brain slices. Action potentials were first detected in a region that corresponded most closely to the unmyelinated axon initial segment, as defined by Golgi and ankyrin G labelling. Following initiation, action potentials propagated reliably into axonal and somatodendritic compartments with conduction velocities of ∼5 m s−1 and ∼0.7 m s−1, respectively. Action potentials generated by neurons with axons truncated within or beyond the axon initial segment were not significantly different. However, axon initial segment and somatic but not dendritic or more distal axonal application of low [Na+] ACSF or the selective Nav channel blocker tetrodotoxin consistently depolarized action potential threshold. Finally, somatodendritic but not axonal application of GABA evoked large, rapid inhibitory currents in concordance with electron microscopic analyses, which revealed that the somatodendritic compartment was the principal target of putative inhibitory inputs. Together the data are consistent with the conclusions that in STN neurons the axon initial segment and soma express an excess of Nav channels for the generation of autonomous activity, while synaptic activation of somatodendritic GABAA receptors regulates the axonal initiation of action potentials. PMID:18832425

Influence of asymmetric attenuation of single and paired dendritic inputs on summation of synaptic potentials and initiation of action potentials.

PubMed

Fortier, Pierre A; Bray, Chelsea

2013-04-16

Previous studies revealed mechanisms of dendritic inputs leading to action potential initiation at the axon initial segment and backpropagation into the dendritic tree. This interest has recently expanded toward the communication between different parts of the dendritic tree which could preprocess information before reaching the soma. This study tested for effects of asymmetric voltage attenuation between different sites in the dendritic tree on summation of synaptic inputs and action potential initiation using the NEURON simulation environment. Passive responses due to the electrical equivalent circuit of the three-dimensional neuron architecture with leak channels were examined first, followed by the responses after adding voltage-gated channels and finally synaptic noise. Asymmetric attenuation of voltage, which is a function of asymmetric input resistance, was seen between all pairs of dendritic sites but the transfer voltages (voltage recorded at the opposite site from stimulation among a pair of dendritic sites) were equal and also summed linearly with local voltage responses during simultaneous stimulation of both sites. In neurons with voltage-gated channels, we reproduced the observations where a brief stimulus to the proximal ascending dendritic branch of a pyramidal cell triggers a local action potential but a long stimulus triggers a somal action potential. Combined stimulation of a pair of sites in this proximal dendrite did not alter this pattern. The attraction of the action potential onset toward the soma with a long stimulus in the absence of noise was due to the higher density of voltage-gated sodium channels at the axon initial segment. This attraction was, however, negligible at the most remote distal dendritic sites and was replaced by an effect due to high input resistance. Action potential onset occurred at the dendritic site of higher input resistance among a pair of remote dendritic sites, irrespective of which of these two sites received the synaptic input. Exploration of the parameter space showed how the gradient of voltage-gated channel densities and input resistances along a dendrite could draw the action potential onset away from the stimulation site. The attraction of action potential onset toward the higher density of voltage-gated channels in the soma during stimulation of the proximal dendrite was, however, reduced after the addition of synaptic noise. Copyright © 2012 IBRO. Published by Elsevier Ltd. All rights reserved.

Ling's Adsorption Theory as a Mechanism of Membrane Potential Generation Observed in Both Living and Nonliving Systems.

PubMed

Tamagawa, Hirohisa; Funatani, Makoto; Ikeda, Kota

2016-01-26

The potential between two electrolytic solutions separated by a membrane impermeable to ions was measured and the generation mechanism of potential measured was investigated. From the physiological point of view, a nonzero membrane potential or action potential cannot be observed across the impermeable membrane. However, a nonzero membrane potential including action potential-like potential was clearly observed. Those observations gave rise to a doubt concerning the validity of currently accepted generation mechanism of membrane potential and action potential of cell. As an alternative theory, we found that the long-forgotten Ling's adsorption theory was the most plausible theory. Ling's adsorption theory suggests that the membrane potential and action potential of a living cell is due to the adsorption of mobile ions onto the adsorption site of cell, and this theory is applicable even to nonliving (or non-biological) system as well as living system. Through this paper, the authors emphasize that it is necessary to reconsider the validity of current membrane theory and also would like to urge the readers to pay keen attention to the Ling's adsorption theory which has for long years been forgotten in the history of physiology.

Effects of acetylcholine and noradrenalin on action potentials of isolated rabbit sinoatrial and atrial myocytes.

PubMed

Verkerk, Arie O; Geuzebroek, Guillaume S C; Veldkamp, Marieke W; Wilders, Ronald

2012-01-01

The autonomic nervous system controls heart rate and contractility through sympathetic and parasympathetic inputs to the cardiac tissue, with acetylcholine (ACh) and noradrenalin (NA) as the chemical transmitters. In recent years, it has become clear that specific Regulators of G protein Signaling proteins (RGS proteins) suppress muscarinic sensitivity and parasympathetic tone, identifying RGS proteins as intriguing potential therapeutic targets. In the present study, we have identified the effects of 1 μM ACh and 1 μM NA on the intrinsic action potentials of sinoatrial (SA) nodal and atrial myocytes. Single cells were enzymatically isolated from the SA node or from the left atrium of rabbit hearts. Action potentials were recorded using the amphotericin-perforated patch-clamp technique in the absence and presence of ACh, NA, or a combination of both. In SA nodal myocytes, ACh increased cycle length and decreased diastolic depolarization rate, whereas NA decreased cycle length and increased diastolic depolarization rate. Both ACh and NA increased maximum upstroke velocity. Furthermore, ACh hyperpolarized the maximum diastolic potential. In atrial myocytes stimulated at 2 Hz, both ACh and NA hyperpolarized the maximum diastolic potential, increased the action potential amplitude, and increased the maximum upstroke velocity. Action potential duration at 50 and 90% repolarization was decreased by ACh, but increased by NA. The effects of both ACh and NA on action potential duration showed a dose dependence in the range of 1-1000 nM, while a clear-cut frequency dependence in the range of 1-4 Hz was absent. Intermediate results were obtained in the combined presence of ACh and NA in both SA nodal and atrial myocytes. Our data uncover the extent to which SA nodal and atrial action potentials are intrinsically dependent on ACh, NA, or a combination of both and may thus guide further experiments with RGS proteins.

Effects of Acetylcholine and Noradrenalin on Action Potentials of Isolated Rabbit Sinoatrial and Atrial Myocytes

PubMed Central

Verkerk, Arie O.; Geuzebroek, Guillaume S. C.; Veldkamp, Marieke W.; Wilders, Ronald

2012-01-01

The autonomic nervous system controls heart rate and contractility through sympathetic and parasympathetic inputs to the cardiac tissue, with acetylcholine (ACh) and noradrenalin (NA) as the chemical transmitters. In recent years, it has become clear that specific Regulators of G protein Signaling proteins (RGS proteins) suppress muscarinic sensitivity and parasympathetic tone, identifying RGS proteins as intriguing potential therapeutic targets. In the present study, we have identified the effects of 1 μM ACh and 1 μM NA on the intrinsic action potentials of sinoatrial (SA) nodal and atrial myocytes. Single cells were enzymatically isolated from the SA node or from the left atrium of rabbit hearts. Action potentials were recorded using the amphotericin-perforated patch-clamp technique in the absence and presence of ACh, NA, or a combination of both. In SA nodal myocytes, ACh increased cycle length and decreased diastolic depolarization rate, whereas NA decreased cycle length and increased diastolic depolarization rate. Both ACh and NA increased maximum upstroke velocity. Furthermore, ACh hyperpolarized the maximum diastolic potential. In atrial myocytes stimulated at 2 Hz, both ACh and NA hyperpolarized the maximum diastolic potential, increased the action potential amplitude, and increased the maximum upstroke velocity. Action potential duration at 50 and 90% repolarization was decreased by ACh, but increased by NA. The effects of both ACh and NA on action potential duration showed a dose dependence in the range of 1–1000 nM, while a clear-cut frequency dependence in the range of 1–4 Hz was absent. Intermediate results were obtained in the combined presence of ACh and NA in both SA nodal and atrial myocytes. Our data uncover the extent to which SA nodal and atrial action potentials are intrinsically dependent on ACh, NA, or a combination of both and may thus guide further experiments with RGS proteins. PMID:22754533

The effects of gentamicin and penicillin/streptomycin on the electrophysiology of human induced pluripotent stem cell-derived cardiomyocytes in manual patch clamp and multi-electrode array system.

PubMed

Hyun, Soo-Wang; Kim, Bo-Ram; Lin, Dan; Hyun, Sung-Ae; Yoon, Seong Shoon; Seo, Joung-Wook

Cell culture media usually contains antibiotics including gentamicin or penicillin/streptomycin (PS) to protect cells from bacterial contamination. However, little is known about the effects of antibiotics on action potential and field potential parameters in human induced pluripotent stem cell-derived cardiomyocytes (hiPSC-CMs). The present study examined the effects of gentamicin (10, 25, and 50μg/ml) and PS (50, 100, and 200U/μg/ml) on electrophysiological activity in spontaneously beating hiPSC-CMs using manual patch clamp and multi-electrode array. We also measured mRNA expression of cardiac ion channels in hiPSC-CMs grown in media with or without gentamicin (25μg/ml) using reverse transcription-polymerase chain reaction. We recorded action potential and field potential of hiPSC-CMs grown in the presence or absence of gentamicin or PS. We also observed action potential parameters in hiPSC-CMs after short-term treatment with these antibiotics. Changes in action potential and field potential parameters were observed in hiPSC-CMs grown in media containing gentamicin or PS. Treatment with PS also affected action potential parameters in hiPSC-CMs. In addition, the mRNA expression of cardiac sodium and potassium ion channels was significantly attenuated in hiPSC-CMs grown in the presence of gentamicin (25μg/ml). The present findings suggested that gentamicin should not be used in the culture media of hiPSC-CMs used for the measurement of electrophysiological parameters. Our findings also suggest that 100U/100μg/ml of PS are the maximum appropriate concentrations of these antibiotics for recording action potential waveform, because they did not influence action potential parameters in these cells. Copyright © 2017. Published by Elsevier Inc.

Beta Function Quintessence Cosmological Parameters and Fundamental Constants I: Power and Inverse Power Law Dark Energy Potentials

NASA Astrophysics Data System (ADS)

Thompson, Rodger I.

2018-04-01

This investigation explores using the beta function formalism to calculate analytic solutions for the observable parameters in rolling scalar field cosmologies. The beta function in this case is the derivative of the scalar ϕ with respect to the natural log of the scale factor a, β (φ )=d φ /d ln (a). Once the beta function is specified, modulo a boundary condition, the evolution of the scalar ϕ as a function of the scale factor is completely determined. A rolling scalar field cosmology is defined by its action which can contain a range of physically motivated dark energy potentials. The beta function is chosen so that the associated "beta potential" is an accurate, but not exact, representation of the appropriate dark energy model potential. The basic concept is that the action with the beta potential is so similar to the action with the model potential that solutions using the beta action are accurate representations of solutions using the model action. The beta function provides an extra equation to calculate analytic functions of the cosmologies parameters as a function of the scale factor that are that are not calculable using only the model action. As an example this investigation uses a quintessence cosmology to demonstrate the method for power and inverse power law dark energy potentials. An interesting result of the investigation is that the Hubble parameter H is almost completely insensitive to the power of the potentials and that ΛCDM is part of the family of quintessence cosmology power law potentials with a power of zero.

Beta function quintessence cosmological parameters and fundamental constants - I. Power and inverse power law dark energy potentials

NASA Astrophysics Data System (ADS)

Thompson, Rodger I.

2018-07-01

This investigation explores using the beta function formalism to calculate analytic solutions for the observable parameters in rolling scalar field cosmologies. The beta function in this case is the derivative of the scalar φ with respect to the natural log of the scale factor a, β (φ)=d φ/d ln (a). Once the beta function is specified, modulo a boundary condition, the evolution of the scalar φ as a function of the scale factor is completely determined. A rolling scalar field cosmology is defined by its action which can contain a range of physically motivated dark energy potentials. The beta function is chosen so that the associated `beta potential' is an accurate, but not exact, representation of the appropriate dark energy model potential. The basic concept is that the action with the beta potential is so similar to the action with the model potential that solutions using the beta action are accurate representations of solutions using the model action. The beta function provides an extra equation to calculate analytic functions of the cosmologies parameters as a function of the scale factor that are not calculable using only the model action. As an example, this investigation uses a quintessence cosmology to demonstrate the method for power and inverse power law dark energy potentials. An interesting result of the investigation is that the Hubble parameter H is almost completely insensitive to the power of the potentials and that Λ cold dark matter is part of the family of quintessence cosmology power-law potentials with a power of zero.

Pulsed magnetic stimulation modifies amplitude of action potentials in vitro via ionic channels-dependent mechanism.

PubMed

Ahmed, Zaghloul; Wieraszko, Andrzej

2015-07-01

This paper investigates the influence of pulsed magnetic fields (PMFs) on amplitude of evoked, compound action potential (CAP) recorded from the segments of sciatic nerve in vitro. PMFs were applied for 30 min at frequency of 0.16 Hz and intensity of 15 mT. In confirmation of our previous reports, PMF exposure enhanced amplitude of CAPs. The effect persisted beyond PMF activation period. As expected, CAP amplitude was attenuated by antagonists of sodium channel, lidocaine, and tetrodotoxin. Depression of the potential by sodium channels antagonists was reversed by subsequent exposure to PMFs. The effect of elevated potassium concentration and veratridine on the action potential was modified by exposure to PMFs as well. Neither inhibitors of protein kinase C and protein kinase A, nor known free radicals scavengers had any effects on PMF action. Possible mechanisms of PMF action are discussed. © 2015 Wiley Periodicals, Inc.

Na and Ca components of action potentials in amphioxus muscle cells

PubMed Central

Hagiwara, S.; Kidokoro, Y.

1971-01-01

1. The ionic mechanism of the action potential produced in lamella-like muscle cells of amphioxus, Branchiostoma californiense, was investigated with intracellular recording and polarization techniques. 2. The resting potential and action potential overshoot in normal saline are -53±5 mV (S.D.) and +29±10 mV (S.D.) respectively. 3. The action potential is eliminated by tetrodotoxin (3 μM) and by replacing NaCl in the saline with Tris-chloride but maintained by replacing Na with Li. 4. After elimination of the normal action potential by tetrodotoxin or replacing Na with Tris, the addition of procaine (7·3 mM) to the external saline makes the membrane capable of producing a regenerative potential change. 5. The peak potential of the regenerative response depends on external Ca concentration in a manner predicted by the Nernst equation with Ca concentrations close to normal. 6. The Ca dependent response is reversibly suppressed by Co or La ions. 7. Similar regenerative responses are obtained when Ca is substituted with Sr or Ba. 8. It is concluded that two independent mechanisms of ionic permeability increase occur in the membrane of amphioxus muscle cell, one to Na and the other to Ca. PMID:5158595

7 CFR 1945.19 - Reporting potential natural disasters and initial actions.

Code of Federal Regulations, 2012 CFR

2012-01-01

... 7 Agriculture 13 2012-01-01 2012-01-01 false Reporting potential natural disasters and initial... Assistance-General § 1945.19 Reporting potential natural disasters and initial actions. (a) Purpose. The purpose of reporting potential natural disasters is to provide a systematic procedure for rapid reporting...

7 CFR 1945.19 - Reporting potential natural disasters and initial actions.

Code of Federal Regulations, 2011 CFR

2011-01-01

... 7 Agriculture 13 2011-01-01 2009-01-01 true Reporting potential natural disasters and initial... Assistance-General § 1945.19 Reporting potential natural disasters and initial actions. (a) Purpose. The purpose of reporting potential natural disasters is to provide a systematic procedure for rapid reporting...

7 CFR 1945.19 - Reporting potential natural disasters and initial actions.

Code of Federal Regulations, 2010 CFR

2010-01-01

... 7 Agriculture 13 2010-01-01 2009-01-01 true Reporting potential natural disasters and initial... Assistance-General § 1945.19 Reporting potential natural disasters and initial actions. (a) Purpose. The purpose of reporting potential natural disasters is to provide a systematic procedure for rapid reporting...

Action potentials recorded from bundles of very thin, gray matter axons in rat cerebellar slices using a grease-gap method.

PubMed

Palani, Damodharan; Pekala, Dobromila; Baginskas, Armantas; Szkudlarek, Hanna; Raastad, Morten

2012-07-15

We investigated the ability of a grease-gap method to record fast and slow changes of the membrane potential from bundles of gray matter axons. Their membrane potentials are of particular interest because these axons are different from most axons that have been investigated using intra-axonal or gap techniques. One of the main differences is that gray matter axons typically have closely spaced presynaptic specializations, called boutons or varicosities, distributed along their entire paths. In response to electrical activation of bundles of parallel fiber axons we were able to record small (128-416μV) but stable signals that we show most likely represented a fraction of the trans-membrane action potentials. A less-than 100% fraction prevents measurements of absolute values for membrane potentials, but the good signal-to-noise ratio (typically 10-16) allows detection of changes in resting membrane potential, action potentials and their after-potentials. Because very little is known about the shape of action potentials and after-potentials in these axons we used several independent methods to make it likely that the grease-gap signal was of intra-axonal origin. We demonstrate the utility of the method by showing that the action potentials in cerebellar parallel fibers and hippocampal Schaffer collaterals had a slowly decaying, depolarized after-potential. The method is ideal for pharmacological tests, which we demonstrate by showing that the slow after-potential was sensitive to 4-AP, and that the membrane potential was reduced by 200μM Ba(2+). Copyright © 2012 Elsevier B.V. All rights reserved.

A device for emulating cuff recordings of action potentials propagating along peripheral nerves.

PubMed

Rieger, Robert; Schuettler, Martin; Chuang, Sheng-Chih

2014-09-01

This paper describes a device that emulates propagation of action potentials along a peripheral nerve, suitable for reproducible testing of bio-potential recording systems using nerve cuff electrodes. The system is a microcontroller-based stand-alone instrument which uses established nerve and electrode models to represent neural activity of real nerves recorded with a nerve cuff interface, taking into consideration electrode impedance, voltages picked up by the electrodes, and action potential propagation characteristics. The system emulates different scenarios including compound action potentials with selectable propagation velocities and naturally occurring nerve traffic from different velocity fiber populations. Measured results from a prototype implementation are reported and compared with in vitro recordings from Xenopus Laevis frog sciatic nerve, demonstrating that the electrophysiological setting is represented to a satisfactory degree, useful for the development, optimization and characterization of future recording systems.

Nerve Impulses in Plants

ERIC Educational Resources Information Center

Blatt, F. J.

1974-01-01

Summarizes research done on the resting and action potential of nerve impulses, electrical excitation of nerve cells, electrical properties of Nitella, and temperature effects on action potential. (GS)

Central Nervous System-Toxic Lidocaine Concentrations Unmask L-Type Ca²⁺ Current-Mediated Action Potentials in Rat Thalamocortical Neurons: An In Vitro Mechanism of Action Study.

PubMed

Putrenko, Igor; Ghavanini, Amer A; Meyer Schöniger, Katrin S; Schwarz, Stephan K W

2016-05-01

High systemic lidocaine concentrations exert well-known toxic effects on the central nervous system (CNS), including seizures, coma, and death. The underlying mechanisms are still largely obscure, and the actions of lidocaine on supraspinal neurons have received comparatively little study. We recently found that lidocaine at clinically neurotoxic concentrations increases excitability mediated by Na-independent, high-threshold (HT) action potential spikes in rat thalamocortical neurons. Our goal in this study was to characterize these spikes and test the hypothesis that they are generated by HT Ca currents, previously implicated in neurotoxicity. We also sought to identify and isolate the specific underlying subtype of Ca current. We investigated the actions of lidocaine in the CNS-toxic concentration range (100 μM-1 mM) on ventrobasal thalamocortical neurons in rat brain slices in vitro, using whole-cell patch-clamp recordings aided by differential interference contrast infrared videomicroscopy. Drugs were bath applied; action potentials were generated using current clamp protocols, and underlying currents were identified and isolated with ion channel blockers and electrolyte substitution. Lidocaine (100 μM-1 mM) abolished Na-dependent tonic firing in all neurons tested (n = 46). However, in 39 of 46 (85%) neurons, lidocaine unmasked evoked HT action potentials with lower amplitudes and rates of de-/repolarization compared with control. These HT action potentials remained during the application of tetrodotoxin (600 nM), were blocked by Cd (50 μM), and disappeared after superfusion with an extracellular solution deprived of Ca. These features implied that the unmasked potentials were generated by high-voltage-activated Ca channels and not by Na channels. Application of the L-type Ca channel blocker, nifedipine (5 μM), completely blocked the HT potentials, whereas the N-type Ca channel blocker, ω-conotoxin GVIA (1 μM), had little effect. At clinically CNS-toxic concentrations, lidocaine unmasked in thalamocortical neurons evoked HT action potentials mediated by the L-type Ca current while substantially suppressing Na-dependent excitability. On the basis of the known role of an increase in intracellular Ca in the pathogenesis of local anesthetic neurotoxicity, this novel action represents a plausible contributing candidate mechanism for lidocaine's CNS toxicity in vivo.

An intracellular analysis of the visual responses of neurones in cat visual cortex.

PubMed Central

Douglas, R J; Martin, K A; Whitteridge, D

1991-01-01

1. Extracellular and intracellular recordings were made from neurones in the visual cortex of the cat in order to compare the subthreshold membrane potentials, reflecting the input to the neurone, with the output from the neurone seen as action potentials. 2. Moving bars and edges, generated under computer control, were used to stimulate the neurones. The membrane potential was digitized and averaged for a number of trials after stripping the action potentials. Comparison of extracellular and intracellular discharge patterns indicated that the intracellular impalement did not alter the neurones' properties. Input resistance of the neurone altered little during stable intracellular recordings (30 min-2 h 50 min). 3. Intracellular recordings showed two distinct patterns of membrane potential changes during optimal visual stimulation. The patterns corresponded closely to the division of S-type (simple) and C-type (complex) receptive fields. Simple cells had a complex pattern of membrane potential fluctuations, involving depolarizations alternating with hyperpolarizations. Complex cells had a simple single sustained plateau of depolarization that was often followed but not preceded by a hyperpolarization. In both simple and complex cells the depolarizations led to action potential discharges. The hyperpolarizations were associated with inhibition of action potential discharge. 4. Stimulating simple cells with non-optimal directions of motion produced little or no hyperpolarization of the membrane in most cases, despite a lack of action potential output. Directional complex cells always produced a single plateau of depolarization leading to action potential discharge in both the optimal and non-optimal directions of motion. The directionality could not be predicted on the basis of the position of the hyperpolarizing inhibitory potentials found in the optimal direction. 5. Stimulation of simple cells with non-optimal orientations occasionally produced slight hyperpolarizations and inhibition of action potential discharge. Complex cells, which had broader orientation tuning than simple cells, could show marked hyperpolarization for non-optimal orientations, but this was not generally the case. 6. The data do not support models of directionality and orientation that rely solely on strong inhibitory mechanisms to produce stimulus selectivity. PMID:1804981

Land Water Storage within the Congo Basin Inferred from GRACE Satellite Gravity Data

NASA Technical Reports Server (NTRS)

Crowley, John W.; Mitrovica, Jerry X.; Bailey, Richard C.; Tamisiea, Mark E.; Davis, James L.

2006-01-01

GRACE satellite gravity data is used to estimate terrestrial (surface plus ground) water storage within the Congo Basin in Africa for the period of April, 2002 - May, 2006. These estimates exhibit significant seasonal (30 +/- 6 mm of equivalent water thickness) and long-term trends, the latter yielding a total loss of approximately 280 km(exp 3) of water over the 50-month span of data. We also combine GRACE and precipitation data set (CMAP, TRMM) to explore the relative contributions of the source term to the seasonal hydrological balance within the Congo Basin. We find that the seasonal water storage tends to saturate for anomalies greater than 30-44 mm of equivalent water thickness. Furthermore, precipitation contributed roughly three times the peak water storage after anomalously rainy seasons, in early 2003 and 2005, implying an approximately 60-70% loss from runoff and evapotranspiration. Finally, a comparison of residual land water storage (monthly estimates minus best-fitting trends) in the Congo and Amazon Basins shows an anticorrelation, in agreement with the 'see-saw' variability inferred by others from runoff data.

Arrangement and Applying of Movement Patterns in the Cerebellum Based on Semi-supervised Learning.

PubMed

Solouki, Saeed; Pooyan, Mohammad

2016-06-01

Biological control systems have long been studied as a possible inspiration for the construction of robotic controllers. The cerebellum is known to be involved in the production and learning of smooth, coordinated movements. Therefore, highly regular structure of the cerebellum has been in the core of attention in theoretical and computational modeling. However, most of these models reflect some special features of the cerebellum without regarding the whole motor command computational process. In this paper, we try to make a logical relation between the most significant models of the cerebellum and introduce a new learning strategy to arrange the movement patterns: cerebellar modular arrangement and applying of movement patterns based on semi-supervised learning (CMAPS). We assume here the cerebellum like a big archive of patterns that has an efficient organization to classify and recall them. The main idea is to achieve an optimal use of memory locations by more than just a supervised learning and classification algorithm. Surely, more experimental and physiological researches are needed to confirm our hypothesis.

Quaternionic Kähler Detour Complexes and {mathcal{N} = 2} Supersymmetric Black Holes

NASA Astrophysics Data System (ADS)

Cherney, D.; Latini, E.; Waldron, A.

2011-03-01

We study a class of supersymmetric spinning particle models derived from the radial quantization of stationary, spherically symmetric black holes of four dimensional {{mathcal N} = 2} supergravities. By virtue of the c-map, these spinning particles move in quaternionic Kähler manifolds. Their spinning degrees of freedom describe mini-superspace-reduced supergravity fermions. We quantize these models using BRST detour complex technology. The construction of a nilpotent BRST charge is achieved by using local (worldline) supersymmetry ghosts to generate special holonomy transformations. (An interesting byproduct of the construction is a novel Dirac operator on the superghost extended Hilbert space.) The resulting quantized models are gauge invariant field theories with fields equaling sections of special quaternionic vector bundles. They underly and generalize the quaternionic version of Dolbeault cohomology discovered by Baston. In fact, Baston’s complex is related to the BPS sector of the models we write down. Our results rely on a calculus of operators on quaternionic Kähler manifolds that follows from BRST machinery, and although directly motivated by black hole physics, can be broadly applied to any model relying on quaternionic geometry.

Staff Handbook on Natural Gas.

ERIC Educational Resources Information Center

Gorges, H. A., Ed.; Raine, L. P., Ed.

The Department of Commerce created a Natural Gas Action Group early in the fall of 1975 to assist industrial firms and the communities they serve to cope with the effects of potentially severe and crippling curtailment situations. This action group was trained to assess a specific local situation, review the potential for remedial action and…

75 FR 43072 - Trichoderma Hamatum Isolate 382; Exemption from the Requirement of a Tolerance

Federal Register 2010, 2011, 2012, 2013, 2014

2010-07-23

... Information A. Does this Action Apply to Me? You may be potentially affected by this action if you are an agricultural producer, food manufacturer, or pesticide manufacturer. Potentially affected entities may include... exhaustive, but rather provides a guide for readers regarding entities likely to be affected by this action...

Remodelling of action potential and intracellular calcium cycling dynamics during subacute myocardial infarction promotes ventricular arrhythmias in Langendorff-perfused rabbit hearts

PubMed Central

Chou, Chung-Chuan; Zhou, Shengmei; Hayashi, Hideki; Nihei, Motoki; Liu, Yen-Bin; Wen, Ming-Shien; Yeh, San-Jou; Fishbein, Michael C; Weiss, James N; Lin, Shien-Fong; Wu, Delon; Chen, Peng-Sheng

2007-01-01

We hypothesize that remodelling of action potential and intracellular calcium (Cai) dynamics in the peri-infarct zone contributes to ventricular arrhythmogenesis in the postmyocardial infarction setting. To test this hypothesis, we performed simultaneous optical mapping of Cai and membrane potential (Vm) in the left ventricle in 15 rabbit hearts with myocardial infarction for 1 week. Ventricular premature beats frequently originated from the peri-infarct zone, and 37% showed elevation of Cai prior to Vm depolarization, suggesting reverse excitation–contraction coupling as their aetiology. During electrically induced ventricular fibrillation, the highest dominant frequency was in the peri-infarct zone in 61 of 70 episodes. The site of highest dominant frequency had steeper action potential duration restitution and was more susceptible to pacing-induced Cai alternans than sites remote from infarct. Wavebreaks during ventricular fibrillation tended to occur at sites of persistently elevated Cai. Infusion of propranolol flattened action potential duration restitution, reduced wavebreaks and converted ventricular fibrillation to ventricular tachycardia. We conclude that in the subacute phase of myocardial infarction, the peri-infarct zone exhibits regions with steep action potential duration restitution slope and unstable Cai dynamics. These changes may promote ventricular extrasystoles and increase the incidence of wavebreaks during ventricular fibrillation. Whereas increased tissue heterogeneity after subacute myocardial infarction creates a highly arrhythmogenic substrate, dynamic action potential and Cai cycling remodelling also contribute to the initiation and maintenance of ventricular fibrillation in this setting. PMID:17272354

Components of action potential repolarization in cerebellar parallel fibres.

PubMed

Pekala, Dobromila; Baginskas, Armantas; Szkudlarek, Hanna J; Raastad, Morten

2014-11-15

Repolarization of the presynaptic action potential is essential for transmitter release, excitability and energy expenditure. Little is known about repolarization in thin, unmyelinated axons forming en passant synapses, which represent the most common type of axons in the mammalian brain's grey matter.We used rat cerebellar parallel fibres, an example of typical grey matter axons, to investigate the effects of K(+) channel blockers on repolarization. We show that repolarization is composed of a fast tetraethylammonium (TEA)-sensitive component, determining the width and amplitude of the spike, and a slow margatoxin (MgTX)-sensitive depolarized after-potential (DAP). These two components could be recorded at the granule cell soma as antidromic action potentials and from the axons with a newly developed miniaturized grease-gap method. A considerable proportion of fast repolarization remained in the presence of TEA, MgTX, or both. This residual was abolished by the addition of quinine. The importance of proper control of fast repolarization was demonstrated by somatic recordings of antidromic action potentials. In these experiments, the relatively broad K(+) channel blocker 4-aminopyridine reduced the fast repolarization, resulting in bursts of action potentials forming on top of the DAP. We conclude that repolarization of the action potential in parallel fibres is supported by at least three groups of K(+) channels. Differences in their temporal profiles allow relatively independent control of the spike and the DAP, whereas overlap of their temporal profiles provides robust control of axonal bursting properties.

Effects of pioglitazone on cardiac ion currents and action potential morphology in canine ventricular myocytes.

PubMed

Kistamás, Kornél; Szentandrássy, Norbert; Hegyi, Bence; Ruzsnavszky, Ferenc; Váczi, Krisztina; Bárándi, László; Horváth, Balázs; Szebeni, Andrea; Magyar, János; Bányász, Tamás; Kecskeméti, Valéria; Nánási, Péter P

2013-06-15

Despite its widespread therapeutical use there is little information on the cellular cardiac effects of the antidiabetic drug pioglitazone in larger mammals. In the present study, therefore, the concentration-dependent effects of pioglitazone on ion currents and action potential configuration were studied in isolated canine ventricular myocytes using standard microelectrode, conventional whole cell patch clamp, and action potential voltage clamp techniques. Pioglitazone decreased the maximum velocity of depolarization and the amplitude of phase-1 repolarization at concentrations ≥3 μM. Action potentials were shortened by pioglitazone at concentrations ≥10 μM, which effect was accompanied with significant reduction of beat-to-beat variability of action potential duration. Several transmembrane ion currents, including the transient outward K(+) current (Ito), the L-type Ca(2+) current (ICa), the rapid and slow components of the delayed rectifier K(+) current (IKr and IKs, respectively), and the inward rectifier K(+) current (IK1) were inhibited by pioglitazone under conventional voltage clamp conditions. Ito was blocked significantly at concentrations ≥3 μM, ICa, IKr, IKs at concentrations ≥10 μM, while IK1 at concentrations ≥30 μM. Suppression of Ito, ICa, IKr, and IK1 has been confirmed also under action potential voltage clamp conditions. ATP-sensitive K(+) current, when activated by lemakalim, was effectively blocked by pioglitazone. Accordingly, action potentials were prolonged by 10 μM pioglitazone when the drug was applied in the presence of lemakalim. All these effects developed rapidly and were readily reversible upon washout. In conclusion, pioglitazone seems to be a harmless agent at usual therapeutic concentrations. Copyright © 2013 Elsevier B.V. All rights reserved.

Activation of cannabinoid CB1 receptors modulates evoked action potentials in rat retinal ganglion cells.

PubMed

Jiang, Shu-Xia; Li, Qian; Wang, Xiao-Han; Li, Fang; Wang, Zhong-Feng

2013-08-25

Activation of cannabinoid CB1 receptors (CB1Rs) regulates a variety of physiological functions in the vertebrate retina through modulating various types of ion channels. The aim of the present study was to investigate the effects of this receptor on cell excitability of rat retinal ganglion cells (RGCs) in retinal slices using whole-cell patch-clamp techniques. The results showed that under current-clamped condition perfusing WIN55212-2 (WIN, 5 μmol/L), a CB1R agonist, did not significantly change the spontaneous firing frequency and resting membrane potential of RGCs. In the presence of cocktail synaptic blockers, including excitatory postsynaptic receptor blockers CNQX and D-APV, and inhibitory receptor blockers bicuculline and strychnine, perfusion of WIN (5 μmol/L) hardly changed the frequencies of evoked action potentials by a series of positive current injection (from +10 to +100 pA). Phase-plane plot analysis showed that both average threshold voltage for triggering action potential and delay time to reach threshold voltage were not affected by WIN. However, WIN significantly decreased +dV/dtmax and -dV/dtmax of action potentials, suggestive of reduced rising and descending velocities of action potentials. The effects of WIN were reversed by co-application of SR141716, a CB1R selective antagonist. Moreover, WIN did not influence resting membrane potential of RGCs with synaptic inputs being blocked. These results suggest that activation of CB1Rs may regulate intrinsic excitability of rat RGCs through modulating evoked action potentials.

Strategies for improving neural signal detection using a neural-electronic interface.

PubMed

Szlavik, Robert B

2003-03-01

There have been various theoretical and experimental studies presented in the literature that focus on interfacing neurons with discrete electronic devices, such as transistors. From both a theoretical and experimental perspective, these studies have emphasized the variability in the characteristics of the detected action potential from the nerve cell. The demonstrated lack of reproducible fidelity of the nerve cell action potential at the device junction would make it impractical to implement these devices in any neural prosthetic application where reliable detection of the action potential was a prerequisite. In this study, the effects of several different physical parameters on the fidelity of the detected action potential at the device junction are investigated and discussed. The impact of variations in the extracellular resistivity, which directly affects the junction seal resistance, is studied along with the impact of variable nerve cell membrane capacitance and variations in the injected charge. These parameters are discussed in the context of their suitability to design manipulation for the purpose of improving the fidelity of the detected neural action potential. In addition to investigating the effects of variations in these parameters, the applicability of the linear equivalent circuit approach to calculating the junction potential is investigated.

Simulation of action potentials from metabolically impaired cardiac myocytes. Role of ATP-sensitive K+ current.

PubMed

Ferrero, J M; Sáiz, J; Ferrero, J M; Thakor, N V

1996-08-01

The role of the ATP-sensitive K+ current (IK-ATP) and its contribution to electrophysiological changes that occur during metabolic impairment in cardiac ventricular myocytes is still being discussed. The aim of this work was to quantitatively study this issue by using computer modeling. A model of IK-ATP is formulated and incorporated into the Luo-Rudy ionic model of the ventricular action potential. Action potentials under different degrees of activation of IK-ATP are simulated. Our results show that in normal ionic concentrations, only approximately 0.6% of the KATP channels, when open, should account for a 50% reduction in action potential duration. However, increased levels of intracellular Mg2+ counteract this shortening. Under conditions of high [K+]0, such as those found in early ischemia, the activation of only approximately 0.4% of the KATP channels could account for a 50% reduction in action potential duration. Thus, our results suggest that opening of IK-ATP channels should play a significant role in action potential shortening during hypoxic/ischemic episodes, with the fraction of open channels involved being very low ( < 1%). However, the results of the model suggest that activation of IK-ATP alone does not quantitatively account for the observed K+ efflux in metabolically impaired cardiac myocytes. Mechanisms other than KATP channel activation should be responsible for a significant part of the K+ efflux measured in hypoxic/ischemic situations.

Peripheral nerve recruitment curve using near-infrared stimulation

NASA Astrophysics Data System (ADS)

Dautrebande, Marie; Doguet, Pascal; Gorza, Simon-Pierre; Delbeke, Jean; Nonclercq, Antoine

2018-02-01

In the context of near-infrared neurostimulation, we report on an experimental hybrid electrode allowing for simultaneous photonic or electrical neurostimulation and for electrical recording of evoked action potentials. The electrode includes three contacts and one optrode. The optrode is an opening in the cuff through which the tip of an optical fibre is held close to the epineurium. Two contacts provide action potential recording. The remaining contact, together with a remote subcutaneous electrode, is used for electric stimulation which allows periodical assessment of the viability of the nerve during the experiment. A 1470 nm light source was used to stimulate a mouse sciatic nerve. Neural action potentials were not successfully recorded because of the electrical noise so muscular activity was used to reflect the motor fibres stimulation. A recruitment curve was obtained by stimulating with photonic pulses of same power and increasing duration and recording the evoked muscular action potentials. Motor fibres can be recruited with radiant exposures between 0.05 and 0.23 J/cm2 for pulses in the 100 to 500 μs range. Successful stimulation at short duration and at a commercial wavelength is encouraging in the prospect of miniaturisation and practical applications. Motor fibres recruitment curve is a first step in an ongoing research work. Neural action potential acquisition will be improved, with aim to shed light on the mechanism of action potential initiation under photonic stimulation.

Action Learning: Avoiding Conflict or Enabling Action

ERIC Educational Resources Information Center

Corley, Aileen; Thorne, Ann

2006-01-01

Action learning is based on the premise that action and learning are inextricably entwined and it is this potential, to enable action, which has contributed to the growth of action learning within education and management development programmes. However has this growth in action learning lead to an evolution or a dilution of Revan's classical…

Action Learning: Potential for Inner City Youth

ERIC Educational Resources Information Center

Epps, Edgar G.

1974-01-01

Working class and minority participation in action-learning poses potential problems likely to be overlooked by program planners. This presentation reveals the trouble spots and offers constructive suggestions. (Editor)

Onset dynamics of action potentials in rat neocortical neurons and identified snail neurons: quantification of the difference.

PubMed

Volgushev, Maxim; Malyshev, Aleksey; Balaban, Pavel; Chistiakova, Marina; Volgushev, Stanislav; Wolf, Fred

2008-04-09

The generation of action potentials (APs) is a key process in the operation of nerve cells and the communication between neurons. Action potentials in mammalian central neurons are characterized by an exceptionally fast onset dynamics, which differs from the typically slow and gradual onset dynamics seen in identified snail neurons. Here we describe a novel method of analysis which provides a quantitative measure of the onset dynamics of action potentials. This method captures the difference between the fast, step-like onset of APs in rat neocortical neurons and the gradual, exponential-like AP onset in identified snail neurons. The quantitative measure of the AP onset dynamics, provided by the method, allows us to perform quantitative analyses of factors influencing the dynamics.

Onset Dynamics of Action Potentials in Rat Neocortical Neurons and Identified Snail Neurons: Quantification of the Difference

PubMed Central

Volgushev, Maxim; Malyshev, Aleksey; Balaban, Pavel; Chistiakova, Marina; Volgushev, Stanislav; Wolf, Fred

2008-01-01

The generation of action potentials (APs) is a key process in the operation of nerve cells and the communication between neurons. Action potentials in mammalian central neurons are characterized by an exceptionally fast onset dynamics, which differs from the typically slow and gradual onset dynamics seen in identified snail neurons. Here we describe a novel method of analysis which provides a quantitative measure of the onset dynamics of action potentials. This method captures the difference between the fast, step-like onset of APs in rat neocortical neurons and the gradual, exponential-like AP onset in identified snail neurons. The quantitative measure of the AP onset dynamics, provided by the method, allows us to perform quantitative analyses of factors influencing the dynamics. PMID:18398478

Effect of Detergent on Electrical Properties of Squid Axon Membrane

PubMed Central

Kishimoto, Uichiro; Adelman, William J.

1964-01-01

The effects of detergents on squid giant axon action and resting potentials as well as membrane conductances in the voltage clamp have been studied. Anionic detergents (sodium lauryl sulfate, 0.1 to 1.0 mM; dimethyl benzene sulfonate, 1 to 20 mM, pH 7.6) cause a temporary increase and a later decrease of action potential height and the value of the resting potential. Cationic detergent (cetyl trimethyl ammonium chloride, 6 x 10-5 M or more, pH 7.6) generally brings about immediate and irreversible decreases in the action and resting potentials. Non-ionic detergent (tween 80, 0.1 M, pH 7.6) causes a slight reversible reduction of action potential height without affecting the value of the resting potential. Both anionic and cationic detergents generally decrease the sodium and potassium conductances irreversibly. The effect of non-ionic detergent is to decrease the sodium conductance reversibly, leaving the potassium conductance almost unchanged. PMID:14158665

The influence of action observation on action execution: Dissociating the contribution of action on perception, perception on action, and resolving conflict.

PubMed

Deschrijver, Eliane; Wiersema, Jan R; Brass, Marcel

2017-04-01

For more than 15 years, motor interference paradigms have been used to investigate the influence of action observation on action execution. Most research on so-called automatic imitation has focused on variables that play a modulating role or investigated potential confounding factors. Interestingly, furthermore, a number of functional magnetic resonance imaging (fMRI) studies have tried to shed light on the functional mechanisms and neural correlates involved in imitation inhibition. However, these fMRI studies, presumably due to poor temporal resolution, have primarily focused on high-level processes and have neglected the potential role of low-level motor and perceptual processes. In the current EEG study, we therefore aimed to disentangle the influence of low-level perceptual and motoric mechanisms from high-level cognitive mechanisms. We focused on potential congruency differences in the visual N190 - a component related to the processing of biological motion, the Readiness Potential - a component related to motor preparation, and the high-level P3 component. Interestingly, we detected congruency effects in each of these components, suggesting that the interference effect in an automatic imitation paradigm is not only related to high-level processes such as self-other distinction but also to more low-level influences of perception on action and action on perception. Moreover, we documented relationships of the neural effects with (autistic) behavior.

Associative, Bidirectional Changes in Neural Signaling Utilizing NMDA Receptor- and Endocannabinoid-Dependent Mechanisms

ERIC Educational Resources Information Center

Li, Qin; Burrell, Brian D.

2011-01-01

Persistent, bidirectional changes in synaptic signaling (that is, potentiation and depression of the synapse) can be induced by the precise timing of individual pre- and postsynaptic action potentials. However, far less attention has been paid to the ability of paired trains of action potentials to elicit persistent potentiation or depression. We…

Final Environmental Assessment: Addressing An Army and Air Force Exchange Service (AAFES) Lifestyle Center at Eglin Air Force Base, Florida

DTIC Science & Technology

2008-11-01

the proposed site has the potential for adverse effects on surface water bodies in the event of a spill or uncontrolled erosion. Implementation of...inclusion of a No Action Alternative against which potential effects can be compared. While the No Action Alternative would not satisfy the purpose... potential effects on project site and adjacent land uses. The foremost factor affecting a proposed action in terms of land use is its compliance

Localization of effective actions in open superstring field theory

NASA Astrophysics Data System (ADS)

Maccaferri, Carlo; Merlano, Alberto

2018-03-01

We consider the construction of the algebraic part of D-branes tree-level effective action from Berkovits open superstring field theory. Applying this construction to the quartic potential of massless fields carrying a specific worldsheet charge, we show that the full contribution to the potential localizes at the boundary of moduli space, reducing to elementary two-point functions. As examples of this general mechanism, we show how the Yang-Mills quartic potential and the instanton effective action of a Dp/D( p - 4) system are reproduced.

77 FR 45535 - Aldicarb; Proposed Tolerance Actions

Federal Register 2010, 2011, 2012, 2013, 2014

2012-08-01

... Aldicarb; Proposed Tolerance Actions AGENCY: Environmental Protection Agency (EPA). ACTION: Proposed rule... Information A. Does this action apply to me? You may be potentially affected by this action if you are an... exhaustive, but rather provides a guide for readers regarding entities likely to be affected by this action...

Sodium and potassium conductance changes during a membrane action potential.

PubMed

Bezanilla, F; Rojas, E; Taylor, R E

1970-12-01

1. A method for turning a membrane potential control system on and off in less than 10 musec is described. This method was used to record membrane currents in perfused giant axons from Dosidicus gigas and Loligo forbesi after turning on the voltage clamp system at various times during the course of a membrane action potential.2. The membrane current measured just after the capacity charging transient was found to have an almost linear relation to the controlled membrane potential.3. The total membrane conductance taken from these current-voltage curves was found to have a time course during the action potential similar to that found by Cole & Curtis (1939).4. The instantaneous current voltage curves were linear enough to make it possible to obtain a good estimate of the individual sodium and potassium channel conductances, either algebraically or by clamping to the sodium, or potassium, reversal potentials. Good general agreement was obtained with the predictions of the Hodgkin-Huxley equations.5. We consider these results to constitute the first direct experimental demonstration of the conductance changes to sodium and potassium during the course of an action potential.

Calcium-Induced Calcium Release during Action Potential Firing in Developing Inner Hair Cells

PubMed Central

Iosub, Radu; Avitabile, Daniele; Grant, Lisa; Tsaneva-Atanasova, Krasimira; Kennedy, Helen J.

2015-01-01

In the mature auditory system, inner hair cells (IHCs) convert sound-induced vibrations into electrical signals that are relayed to the central nervous system via auditory afferents. Before the cochlea can respond to normal sound levels, developing IHCs fire calcium-based action potentials that disappear close to the onset of hearing. Action potential firing triggers transmitter release from the immature IHC that in turn generates experience-independent firing in auditory neurons. These early signaling events are thought to be essential for the organization and development of the auditory system and hair cells. A critical component of the action potential is the rise in intracellular calcium that activates both small conductance potassium channels essential during membrane repolarization, and triggers transmitter release from the cell. Whether this calcium signal is generated by calcium influx or requires calcium-induced calcium release (CICR) is not yet known. IHCs can generate CICR, but to date its physiological role has remained unclear. Here, we used high and low concentrations of ryanodine to block or enhance CICR to determine whether calcium release from intracellular stores affected action potential waveform, interspike interval, or changes in membrane capacitance during development of mouse IHCs. Blocking CICR resulted in mixed action potential waveforms with both brief and prolonged oscillations in membrane potential and intracellular calcium. This mixed behavior is captured well by our mathematical model of IHC electrical activity. We perform two-parameter bifurcation analysis of the model that predicts the dependence of IHCs firing patterns on the level of activation of two parameters, the SK2 channels activation and CICR rate. Our data show that CICR forms an important component of the calcium signal that shapes action potentials and regulates firing patterns, but is not involved directly in triggering exocytosis. These data provide important insights into the calcium signaling mechanisms involved in early developmental processes. PMID:25762313

Calcium-Induced calcium release during action potential firing in developing inner hair cells.

PubMed

Iosub, Radu; Avitabile, Daniele; Grant, Lisa; Tsaneva-Atanasova, Krasimira; Kennedy, Helen J

2015-03-10

In the mature auditory system, inner hair cells (IHCs) convert sound-induced vibrations into electrical signals that are relayed to the central nervous system via auditory afferents. Before the cochlea can respond to normal sound levels, developing IHCs fire calcium-based action potentials that disappear close to the onset of hearing. Action potential firing triggers transmitter release from the immature IHC that in turn generates experience-independent firing in auditory neurons. These early signaling events are thought to be essential for the organization and development of the auditory system and hair cells. A critical component of the action potential is the rise in intracellular calcium that activates both small conductance potassium channels essential during membrane repolarization, and triggers transmitter release from the cell. Whether this calcium signal is generated by calcium influx or requires calcium-induced calcium release (CICR) is not yet known. IHCs can generate CICR, but to date its physiological role has remained unclear. Here, we used high and low concentrations of ryanodine to block or enhance CICR to determine whether calcium release from intracellular stores affected action potential waveform, interspike interval, or changes in membrane capacitance during development of mouse IHCs. Blocking CICR resulted in mixed action potential waveforms with both brief and prolonged oscillations in membrane potential and intracellular calcium. This mixed behavior is captured well by our mathematical model of IHC electrical activity. We perform two-parameter bifurcation analysis of the model that predicts the dependence of IHCs firing patterns on the level of activation of two parameters, the SK2 channels activation and CICR rate. Our data show that CICR forms an important component of the calcium signal that shapes action potentials and regulates firing patterns, but is not involved directly in triggering exocytosis. These data provide important insights into the calcium signaling mechanisms involved in early developmental processes. Copyright © 2015 Biophysical Society. Published by Elsevier Inc. All rights reserved.

Power-Law Dynamics of Membrane Conductances Increase Spiking Diversity in a Hodgkin-Huxley Model.

PubMed

Teka, Wondimu; Stockton, David; Santamaria, Fidel

2016-03-01

We studied the effects of non-Markovian power-law voltage dependent conductances on the generation of action potentials and spiking patterns in a Hodgkin-Huxley model. To implement slow-adapting power-law dynamics of the gating variables of the potassium, n, and sodium, m and h, conductances we used fractional derivatives of order η≤1. The fractional derivatives were used to solve the kinetic equations of each gate. We systematically classified the properties of each gate as a function of η. We then tested if the full model could generate action potentials with the different power-law behaving gates. Finally, we studied the patterns of action potential that emerged in each case. Our results show the model produces a wide range of action potential shapes and spiking patterns in response to constant current stimulation as a function of η. In comparison with the classical model, the action potential shapes for power-law behaving potassium conductance (n gate) showed a longer peak and shallow hyperpolarization; for power-law activation of the sodium conductance (m gate), the action potentials had a sharp rise time; and for power-law inactivation of the sodium conductance (h gate) the spikes had wider peak that for low values of η replicated pituitary- and cardiac-type action potentials. With all physiological parameters fixed a wide range of spiking patterns emerged as a function of the value of the constant input current and η, such as square wave bursting, mixed mode oscillations, and pseudo-plateau potentials. Our analyses show that the intrinsic memory trace of the fractional derivative provides a negative feedback mechanism between the voltage trace and the activity of the power-law behaving gate variable. As a consequence, power-law behaving conductances result in an increase in the number of spiking patterns a neuron can generate and, we propose, expand the computational capacity of the neuron.

Method and Early Results of Applying the Global Land Data Assimilation System (GLDAS) in the Third Global Reanalysis of NCEP

NASA Astrophysics Data System (ADS)

Meng, J.; Mitchell, K.; Wei, H.; Yang, R.; Kumar, S.; Geiger, J.; Xie, P.

2008-05-01

Over the past several years, the Environmental Modeling Center (EMC) of the National Centers for Environmental Prediction (NCEP) of the U.S. National Weather Service has developed a Global Land Data Assimilation System (GLDAS). For its computational infrastructure, the GLDAS applies the NASA Land Information System (LIS), developed by the Hydrological Science Branch of NASA Goddard Space Flight Center. The land model utilized in the NCEP GLDAS is the NCEP Noah Land Surface Model (Noah LSM). This presentation will 1) describe how the GLDAS component has been included in the development of NCEP's third global reanalysis (with special attention to the input sources of global precipitation), and 2) will present results from the GLDAS component of pilot tests of the new NCEP global reanalysis. Unlike NCEP's past two global reanalysis projects, this new NCEP global reanalysis includes both a global land data assimilation system (GLDAS) and a global ocean data assimilation system (GODAS). The new global reanalysis will span 30-years (1979-2008) and will include a companion realtime operational component. The atmospheric, ocean, and land states of this global reanalysis will provide the initial conditions for NCEP's 3rd- generation global coupled Climate Forecast System (CFS). NCEP is now preparing to launch a 28-year seasonal reforecast project with its new CFS, to provide the reforecast foundation for operational NCEP seasonal climate forecasts using the new CFS. Together, the new global reanalysis and companion CFS reforecasts constitute what NCEP calls the Climate Forecast System Reanalysis and Reforecast (CFSRR) project. Compared to the previous two generations of NCEP global reanalysis, the hallmark of the GLDAS component of CFSRR is GLDAS use of global analyses of observed precipitation to drive the land surface component of the reanalysis (rather than the typical reanalysis approach of using precipitation from the assimilating background atmospheric model). Specifically, the GLDAS merges two global analyses of observed precipitation produced by the Climate Prediction Center (CPC) of NCEP, as follows: 1) a new CPC daily gauge-only land-only global precipitation analysis at 0.5-degree resolution and 2) the well-known CPC CMAP global 2.0 x 2.5 degree 5-day precipitation analysis, which utilizes satellite estimates of precipitation, as well as some gauge observations. The presentation will describe how these two analyses are merged with latitude-dependent weights that favor the gauge-only analysis in mid-latitudes and the satellite-dominated CMAP analysis in tropical latitudes. Finally, we will show some impacts of using GLDAS to initialize the land states of seasonal CFS reforecasts, versus using the previous generation of NCEP global reanalysis as the source for CFS initial land states.

Coastal system mapping: a new approach to formalising and conceptualising the connectivity of large-scale coastal systems

NASA Astrophysics Data System (ADS)

French, J.; Burningham, H.; Whitehouse, R.

2010-12-01

The concept of the coastal sediment cell has proved invaluable as a basis for estimating sediment budgets and as a framework for coastal management. However, whilst coastal sediment cells are readily identified on compartmentalised coastlines dominated by beach-grade material, the cell concept is less suited to handling broader linkages between estuarine, coastal and offshore systems, and for incorporating longer-range suspended sediment transport. We present a new approach to the conceptualisation of large-scale coastal geomorphic systems based on a hierarchical classification of component landforms and management interventions and mapping of the interactions between them. Coastal system mapping is founded on a classification that identifies high-level landform features, low-level landform elements and engineering interventions. Geomorphic features define the large-scale organisation of a system and include landforms that define gross coastal configuration (e.g. headland, bay) as well as fluvial, estuarine and offshore sub-systems that exchange sediment with and influence the open coast. Detailed system structure is mapped out with reference to a larger set of geomorphic elements (e.g. cliff, dune, beach ridge). Element-element interactions define cross-shore linkages (conceptualised as hinterland, backshore and foreshore zones) and alongshore system structure. Both structural and non-structural engineering interventions are also represented at this level. Element-level mapping is rationalised to represent alongshore variation using as few elements as possible. System linkages include both sediment transfer pathways and influences not associated with direct mass transfer (e.g. effect of a jetty at an inlet). A formal procedure for capturing and graphically representing coastal system structure has been developed around free concept mapping software, CmapTools (http://cmap.ihmc.us). Appended meta-data allow geographic coordinates, data, images and literature pertaining to specific locations to be embedded in system maps. Exported maps can be analysed separately to quantify abundance of system components and their scales of interaction. Our approach is demonstrated for different scales and geomorphic contexts in the UK, including Alnmouth Bay (NE England; 15km), Lowestoft to Felixstowe (E England; 73km) and Cardigan Bay (Wales; 267km). Aerial imagery provides the primary basis for identifying features and elements and likely modes of interaction. This interpretation is then checked against relevant research literature and site data. Coastal system mapping is a kind of knowledge formalisation that generalises disparate sources of information (‘plain data’) into usable knowledge. Consensus-derived system maps are highly effective as a catalyst for structured discussion of geomorphic system behaviour and its implications for coastal management. They also function as a repository for results from quantitative analyses and modelling.

Improved outcomes in auditory brainstem implantation with the use of near-field electrical compound action potentials.

PubMed

Mandalà, Marco; Colletti, Liliana; Colletti, Giacomo; Colletti, Vittorio

2014-12-01

To compare the outcomes (auditory threshold and open-set speech perception at 48-month follow-up) of a new near-field monitoring procedure, electrical compound action potential, on positioning the auditory brainstem implant electrode array on the surface of the cochlear nuclei versus the traditional far-field electrical auditory brainstem response. Retrospective study. Tertiary referral center. Among the 202 patients with auditory brainstem implants fitted and monitored with electrical auditory brainstem response during implant fitting, 9 also underwent electrical compound action potential recording. These subjects were matched retrospectively with a control group of 9 patients in whom only the electrical auditory brainstem response was recorded. Electrical compound action potentials were obtained using a cotton-wick recording electrode located near the surface of the cochlear nuclei and on several cranial nerves. Significantly lower potential thresholds were observed with the recording electrode located on the cochlear nuclei surface compared with the electrical auditory brainstem response (104.4 ± 32.5 vs 158.9 ± 24.2, P = .0030). Electrical brainstem response and compound action potentials identified effects on the neighboring cranial nerves on 3.2 ± 2.4 and 7.8 ± 3.2 electrodes, respectively (P = .0034). Open-set speech perception outcomes at 48-month follow-up had improved significantly in the near- versus far-field recording groups (78.9% versus 56.7%; P = .0051). Electrical compound action potentials during auditory brainstem implantation significantly improved the definition of the potential threshold and the number of auditory and extra-auditory waves generated. It led to the best coupling between the electrode array and cochlear nuclei, significantly improving the overall open-set speech perception. © American Academy of Otolaryngology—Head and Neck Surgery Foundation 2014.

Dofetilide promotes repolarization abnormalities in perfused Guinea-pig heart.

PubMed

Osadchii, Oleg E

2012-12-01

Dofetilide is class III antiarrhythmic agent which prolongs cardiac action potential duration because of selective inhibition of I (Kr), the rapid component of the delayed rectifier K(+) current. Although clinical studies reported on proarrhythmic risk associated with dofetilide treatment, the contributing electrophysiological mechanisms remain poorly understood. This study was designed to determine if dofetilide-induced proarrhythmia may be attributed to abnormalities in ventricular repolarization and refractoriness. The monophasic action potential duration and effective refractory periods (ERP) were assessed at distinct epicardial and endocardial sites along with volume-conducted ECG recordings in isolated, perfused guinea-pig heart preparations. Dofetilide was found to produce the reverse rate-dependent prolongation of ventricular repolarization, increased the steepness of action potential duration rate adaptation, and amplified transepicardial variability in electrical restitution kinetics. Dofetilide also prolonged the T peak-to-end interval on ECG, and elicited a greater prolongation of endocardial than epicardial ERP, thereby increasing transmural dispersion of refractoriness. At epicardium, dofetilide prolonged action potential duration to a greater extent than ERP, thus extending the critical interval for ventricular re-excitation. This change was associated with triangulation of epicardial action potential because of greater dofetilide-induced prolonging effect at 90 % than 30 % repolarization. Premature ectopic beats and spontaneous short-lasting episodes of monomorphic ventricular tachycardia were observed in 44 % of dofetilide-treated heart preparations. Proarrhythmic potential of dofetilide in guinea-pig heart is attributed to steepened electrical restitution, increased transepicardial variability in electrical restitution kinetics, amplified transmural dispersion of refractoriness, increased critical interval for ventricular re-excitation, and triangulation of epicardial action potential.

DBI potential, DBI inflation action and general Lagrangian relative to phantom, K-essence and quintessence

DOE Office of Scientific and Technical Information (OSTI.GOV)

Zhang, Qing; Huang, Yong-Chang, E-mail: ychuang@bjut.edu.cn

We derive a Dirac-Born-Infeld (DBI) potential and DBI inflation action by rescaling the metric. The determinant of the induced metric naturally includes the kinetic energy and the potential energy. In particular, the potential energy and kinetic energy can convert into each other in any order, which is in agreement with the limit of classical physics. This is quite different from the usual DBI action. We show that the Taylor expansion of the DBI action can be reduced into the form in the non-linear classical physics. These investigations are the support for the statement that the results of string theory aremore » consistent with quantum mechanics and classical physics. We deduce the Phantom, K-essence, Quintessence and Generalized Klein-Gordon Equation from the DBI model.« less

An Integrated Circuit for Simultaneous Extracellular Electrophysiology Recording and Optogenetic Neural Manipulation.

PubMed

Chen, Chang Hao; McCullagh, Elizabeth A; Pun, Sio Hang; Mak, Peng Un; Vai, Mang I; Mak, Pui In; Klug, Achim; Lei, Tim C

2017-03-01

The ability to record and to control action potential firing in neuronal circuits is critical to understand how the brain functions. The objective of this study is to develop a monolithic integrated circuit (IC) to record action potentials and simultaneously control action potential firing using optogenetics. A low-noise and high input impedance (or low input capacitance) neural recording amplifier is combined with a high current laser/light-emitting diode (LED) driver in a single IC. The low input capacitance of the amplifier (9.7 pF) was achieved by adding a dedicated unity gain stage optimized for high impedance metal electrodes. The input referred noise of the amplifier is [Formula: see text], which is lower than the estimated thermal noise of the metal electrode. Thus, the action potentials originating from a single neuron can be recorded with a signal-to-noise ratio of at least 6.6. The LED/laser current driver delivers a maximum current of 330 mA, which is adequate for optogenetic control. The functionality of the IC was tested with an anesthetized Mongolian gerbil and auditory stimulated action potentials were recorded from the inferior colliculus. Spontaneous firings of fifth (trigeminal) nerve fibers were also inhibited using the optogenetic protein Halorhodopsin. Moreover, a noise model of the system was derived to guide the design. A single IC to measure and control action potentials using optogenetic proteins is realized so that more complicated behavioral neuroscience research and the translational neural disorder treatments become possible in the future.

Action Potential Dynamics in Fine Axons Probed with an Axonally Targeted Optical Voltage Sensor.

PubMed

Ma, Yihe; Bayguinov, Peter O; Jackson, Meyer B

2017-01-01

The complex and malleable conduction properties of axons determine how action potentials propagate through extensive axonal arbors to reach synaptic terminals. The excitability of axonal membranes plays a major role in neural circuit function, but because most axons are too thin for conventional electrical recording, their properties remain largely unexplored. To overcome this obstacle, we used a genetically encoded hybrid voltage sensor (hVOS) harboring an axonal targeting motif. Expressing this probe in transgenic mice enabled us to monitor voltage changes optically in two populations of axons in hippocampal slices, the large axons of dentate granule cells (mossy fibers) in the stratum lucidum of the CA3 region and the much finer axons of hilar mossy cells in the inner molecular layer of the dentate gyrus. Action potentials propagated with distinct velocities in each type of axon. Repetitive firing broadened action potentials in both populations, but at an intermediate frequency the degree of broadening differed. Repetitive firing also attenuated action potential amplitudes in both mossy cell and granule cell axons. These results indicate that the features of use-dependent action potential broadening, and possible failure, observed previously in large nerve terminals also appear in much finer unmyelinated axons. Subtle differences in the frequency dependences could influence the propagation of activity through different pathways to excite different populations of neurons. The axonally targeted hVOS probe used here opens up the diverse repertoire of neuronal processes to detailed biophysical study.

The marketing potential of corporate social responsibility activities: the case of the alcohol industry in Latin America and the Caribbean.

PubMed

Pantani, Daniela; Peltzer, Raquel; Cremonte, Mariana; Robaina, Katherine; Babor, Thomas; Pinsky, Ilana

2017-01-01

The aims were to: (1) identify, monitor and analyse the Corporate Social Responsibility (CSR) practices of the alcohol industry in Latin America and the Caribbean (LAC) and (2) examine whether the alcohol industry is using these actions to market their products and brands. Nine health experts from Argentina, Brazil and Uruguay conducted a content analysis of 218 CSR activities using a standardized protocol. A content rating procedure was used to evaluate the marketing potential of CSR activities as well as their probable population reach and effectiveness. The LEAD procedure (longitudinal, expert and all data) was applied to verify the accuracy of industry-reported descriptions. A total of 55.8% of the actions were found to have a marketing potential, based on evidence that they are likely to promote brands and products. Actions with marketing potential were more likely to reach a larger audience than actions classified with no marketing potential. Most actions did not fit into any category recommended by the World Health Organization; 50% of the actions involving classroom and college education for young people were found to have marketing potential; 62.3% were classified as meeting the definition of risk management CSR. Alcohol industry Corporate Social Responsibility activities in Latin America and the Caribbean appear to have a strategic marketing role beyond their stated philanthropic and public health purpose. © 2016 Society for the Study of Addiction.

76 FR 40811 - Maneb; Tolerance Actions

Federal Register 2010, 2011, 2012, 2013, 2014

2011-07-12

...; Tolerance Actions AGENCY: Environmental Protection Agency (EPA). ACTION: Final rule. SUMMARY: EPA is... established a docket for this action under docket identification (ID) number EPA-HQ-OPP-2010-0327. All... . SUPPLEMENTARY INFORMATION: I. General Information A. Does this action apply to me? You may be potentially...

Through a Feminist Poststructuralist Lens: Embodied Subjectivites and Participatory Action Research

ERIC Educational Resources Information Center

Chesnay, Catherine T.

2016-01-01

An emerging literature has been building bridges between poststructuralism and participatory action research, highlighting the latter's potential for transformative action. Using examples from participative action research projects with incarcerated or previously incarcerated women, this article discusses how participatory action research is a…

77 FR 18748 - Dicloran and Formetanate; Proposed Tolerance Actions

Federal Register 2010, 2011, 2012, 2013, 2014

2012-03-28

... Dicloran and Formetanate; Proposed Tolerance Actions AGENCY: Environmental Protection Agency (EPA). ACTION... . SUPPLEMENTARY INFORMATION: I. General Information A. Does this action apply to me? You may be potentially affected by this action if you are an agricultural producer, food manufacturer, or pesticide manufacturer...

Differential regulation of GnRH secretion in the preoptic area (POA) and the median eminence (ME) in male mice.

PubMed

Glanowska, Katarzyna M; Moenter, Suzanne M

2015-01-01

GnRH release in the median eminence (ME) is the central output for control of reproduction. GnRH processes in the preoptic area (POA) also release GnRH. We examined region-specific regulation of GnRH secretion using fast-scan cyclic voltammetry to detect GnRH release in brain slices from adult male mice. Blocking endoplasmic reticulum calcium reuptake to elevate intracellular calcium evokes GnRH release in both the ME and POA. This release is action potential dependent in the ME but not the POA. Locally applied kisspeptin induced GnRH secretion in both the ME and POA. Local blockade of inositol triphospate-mediated calcium release inhibited kisspeptin-induced GnRH release in the ME, but broad blockade was required in the POA. In contrast, kisspeptin-evoked secretion in the POA was blocked by local gonadotropin-inhibitory hormone, but broad gonadotropin-inhibitory hormone application was required in the ME. Although action potentials are required for GnRH release induced by pharmacologically-increased intracellular calcium in the ME and kisspeptin-evoked release requires inositol triphosphate-mediated calcium release, blocking action potentials did not inhibit kisspeptin-induced GnRH release in the ME. Kisspeptin-induced GnRH release was suppressed after blocking both action potentials and plasma membrane Ca(2+) channels. This suggests that kisspeptin action in the ME requires both increased intracellular calcium and influx from the outside of the cell but not action potentials. Local interactions among kisspeptin and GnRH processes in the ME could thus stimulate GnRH release without involving perisomatic regions of GnRH neurons. Coupling between action potential generation and hormone release in GnRH neurons is thus likely physiologically labile and may vary with region.

Amphetamine elevates nucleus accumbens dopamine via an action potential-dependent mechanism that is modulated by endocannabinoids

PubMed Central

Covey, Dan P.; Bunner, Kendra D.; Schuweiler, Douglas R.; Cheer, Joseph F.; Garris, Paul A.

2018-01-01

The reinforcing effects of abused drugs are mediated by their ability to elevate nucleus accumbens dopamine. Amphetamine (AMPH) was historically thought to increase dopamine by an action potential-independent, non-exocytotic type of release called efflux, involving reversal of dopamine transporter function and driven by vesicular dopamine depletion. Growing evidence suggests that AMPH also acts by an action potential-dependent mechanism. Indeed, fast-scan cyclic voltammetry demonstrates that AMPH activates dopamine transients, reward-related phasic signals generated by burst firing of dopamine neurons and dependent on intact vesicular dopamine. Not established for AMPH but indicating a shared mechanism, endocannabinoids facilitate this activation of dopamine transients by broad classes of abused drugs. Here, using fast-scan cyclic voltammetry coupled to pharmacological manipulations in awake rats, we investigated the action potential and endocannabinoid dependence of AMPH-induced elevations in nucleus accumbens dopamine. AMPH increased the frequency, amplitude and duration of transients, which were observed riding on top of slower dopamine increases. Surprisingly, silencing dopamine neuron firing abolished all AMPH-induced dopamine elevations, identifying an action potential-dependent origin. Blocking cannabinoid type 1 receptors prevented AMPH from increasing transient frequency, similar to reported effects on other abused drugs, but not from increasing transient duration and inhibiting dopamine uptake. Thus, AMPH elevates nucleus accumbens dopamine by eliciting transients via cannabinoid type 1 receptors and promoting the summation of temporally coincident transients, made more numerous, larger and wider by AMPH. Collectively, these findings are inconsistent with AMPH eliciting action potential-independent dopamine efflux and vesicular dopamine depletion, and support endocannabinoids facilitating phasic dopamine signalling as a common action in drug reinforcement. PMID:27038339

Amphetamine elevates nucleus accumbens dopamine via an action potential-dependent mechanism that is modulated by endocannabinoids.

PubMed

Covey, Dan P; Bunner, Kendra D; Schuweiler, Douglas R; Cheer, Joseph F; Garris, Paul A

2016-06-01

The reinforcing effects of abused drugs are mediated by their ability to elevate nucleus accumbens dopamine. Amphetamine (AMPH) was historically thought to increase dopamine by an action potential-independent, non-exocytotic type of release called efflux, involving reversal of dopamine transporter function and driven by vesicular dopamine depletion. Growing evidence suggests that AMPH also acts by an action potential-dependent mechanism. Indeed, fast-scan cyclic voltammetry demonstrates that AMPH activates dopamine transients, reward-related phasic signals generated by burst firing of dopamine neurons and dependent on intact vesicular dopamine. Not established for AMPH but indicating a shared mechanism, endocannabinoids facilitate this activation of dopamine transients by broad classes of abused drugs. Here, using fast-scan cyclic voltammetry coupled to pharmacological manipulations in awake rats, we investigated the action potential and endocannabinoid dependence of AMPH-induced elevations in nucleus accumbens dopamine. AMPH increased the frequency, amplitude and duration of transients, which were observed riding on top of slower dopamine increases. Surprisingly, silencing dopamine neuron firing abolished all AMPH-induced dopamine elevations, identifying an action potential-dependent origin. Blocking cannabinoid type 1 receptors prevented AMPH from increasing transient frequency, similar to reported effects on other abused drugs, but not from increasing transient duration and inhibiting dopamine uptake. Thus, AMPH elevates nucleus accumbens dopamine by eliciting transients via cannabinoid type 1 receptors and promoting the summation of temporally coincident transients, made more numerous, larger and wider by AMPH. Collectively, these findings are inconsistent with AMPH eliciting action potential-independent dopamine efflux and vesicular dopamine depletion, and support endocannabinoids facilitating phasic dopamine signalling as a common action in drug reinforcement. © 2016 Federation of European Neuroscience Societies and John Wiley & Sons Ltd.

Naturalistic stimulation changes the dynamic response of action potential encoding in a mechanoreceptor

PubMed Central

Pfeiffer, Keram; French, Andrew S.

2015-01-01

Naturalistic signals were created from vibrations made by locusts walking on a Sansevieria plant. Both naturalistic and Gaussian noise signals were used to mechanically stimulate VS-3 slit-sense mechanoreceptor neurons of the spider, Cupiennius salei, with stimulus amplitudes adjusted to give similar firing rates for either stimulus. Intracellular microelectrodes recorded action potentials, receptor potential, and receptor current, using current clamp and voltage clamp. Frequency response analysis showed that naturalistic stimulation contained relatively more power at low frequencies, and caused increased neuronal sensitivity to higher frequencies. In contrast, varying the amplitude of Gaussian stimulation did not change neuronal dynamics. Naturalistic stimulation contained less entropy than Gaussian, but signal entropy was higher than stimulus in the resultant receptor current, indicating addition of uncorrelated noise during transduction. The presence of added noise was supported by measuring linear information capacity in the receptor current. Total entropy and information capacity in action potentials produced by either stimulus were much lower than in earlier stages, and limited to the maximum entropy of binary signals. We conclude that the dynamics of action potential encoding in VS-3 neurons are sensitive to the form of stimulation, but entropy and information capacity of action potentials are limited by firing rate. PMID:26578975

Noise Enhances Action Potential Generation in Mouse Sensory Neurons via Stochastic Resonance.

PubMed

Onorato, Irene; D'Alessandro, Giuseppina; Di Castro, Maria Amalia; Renzi, Massimiliano; Dobrowolny, Gabriella; Musarò, Antonio; Salvetti, Marco; Limatola, Cristina; Crisanti, Andrea; Grassi, Francesca

2016-01-01

Noise can enhance perception of tactile and proprioceptive stimuli by stochastic resonance processes. However, the mechanisms underlying this general phenomenon remain to be characterized. Here we studied how externally applied noise influences action potential firing in mouse primary sensory neurons of dorsal root ganglia, modelling a basic process in sensory perception. Since noisy mechanical stimuli may cause stochastic fluctuations in receptor potential, we examined the effects of sub-threshold depolarizing current steps with superimposed random fluctuations. We performed whole cell patch clamp recordings in cultured neurons of mouse dorsal root ganglia. Noise was added either before and during the step, or during the depolarizing step only, to focus onto the specific effects of external noise on action potential generation. In both cases, step + noise stimuli triggered significantly more action potentials than steps alone. The normalized power norm had a clear peak at intermediate noise levels, demonstrating that the phenomenon is driven by stochastic resonance. Spikes evoked in step + noise trials occur earlier and show faster rise time as compared to the occasional ones elicited by steps alone. These data suggest that external noise enhances, via stochastic resonance, the recruitment of transient voltage-gated Na channels, responsible for action potential firing in response to rapid step-wise depolarizing currents.

Noise Enhances Action Potential Generation in Mouse Sensory Neurons via Stochastic Resonance

PubMed Central

Onorato, Irene; D'Alessandro, Giuseppina; Di Castro, Maria Amalia; Renzi, Massimiliano; Dobrowolny, Gabriella; Musarò, Antonio; Salvetti, Marco; Limatola, Cristina; Crisanti, Andrea; Grassi, Francesca

2016-01-01

Noise can enhance perception of tactile and proprioceptive stimuli by stochastic resonance processes. However, the mechanisms underlying this general phenomenon remain to be characterized. Here we studied how externally applied noise influences action potential firing in mouse primary sensory neurons of dorsal root ganglia, modelling a basic process in sensory perception. Since noisy mechanical stimuli may cause stochastic fluctuations in receptor potential, we examined the effects of sub-threshold depolarizing current steps with superimposed random fluctuations. We performed whole cell patch clamp recordings in cultured neurons of mouse dorsal root ganglia. Noise was added either before and during the step, or during the depolarizing step only, to focus onto the specific effects of external noise on action potential generation. In both cases, step + noise stimuli triggered significantly more action potentials than steps alone. The normalized power norm had a clear peak at intermediate noise levels, demonstrating that the phenomenon is driven by stochastic resonance. Spikes evoked in step + noise trials occur earlier and show faster rise time as compared to the occasional ones elicited by steps alone. These data suggest that external noise enhances, via stochastic resonance, the recruitment of transient voltage-gated Na channels, responsible for action potential firing in response to rapid step-wise depolarizing currents. PMID:27525414

Generation of action potentials in a mathematical model of corticotrophs.

PubMed Central

LeBeau, A P; Robson, A B; McKinnon, A E; Donald, R A; Sneyd, J

1997-01-01

Corticotropin-releasing hormone (CRH) is an important regulator of adrenocorticotropin (ACTH) secretion from pituitary corticotroph cells. The intracellular signaling system that underlies this process involves modulation of voltage-sensitive Ca2+ channel activity, which leads to the generation of Ca2+ action potentials and influx of Ca2+. However, the mechanisms by which Ca2+ channel activity is modulated in corticotrophs are not currently known. We investigated this process in a Hodgkin-Huxley-type mathematical model of corticotroph plasma membrane electrical responses. We found that an increase in the L-type Ca2+ current was sufficient to generate action potentials from a previously resting state of the model. The increase in the L-type current could be elicited by either a shift in the voltage dependence of the current toward more negative potentials, or by an increase in the conductance of the current. Although either of these mechanisms is potentially responsible for the generation of action potentials, previous experimental evidence favors the former mechanism, with the magnitude of the shift required being consistent with the experimental findings. The model also shows that the T-type Ca2+ current plays a role in setting the excitability of the plasma membrane, but does not appear to contribute in a dynamic manner to action potential generation. Inhibition of a K+ conductance that is active at rest also affects the excitability of the plasma membrane. PMID:9284294

High-fidelity optical reporting of neuronal electrical activity with an ultrafast fluorescent voltage sensor

PubMed Central

St-Pierre, François; Marshall, Jesse D; Yang, Ying; Gong, Yiyang; Schnitzer, Mark J; Lin, Michael Z

2015-01-01

Accurate optical reporting of electrical activity in genetically defined neuronal populations is a long-standing goal in neuroscience. Here we describe Accelerated Sensor of Action Potentials 1 (ASAP1), a novel voltage sensor design in which a circularly permuted green fluorescent protein is inserted within an extracellular loop of a voltage-sensing domain, rendering fluorescence responsive to membrane potential. ASAP1 demonstrates on- and off- kinetics of 2.1 and 2.0 ms, reliably detects single action potentials and subthreshold potential changes, and tracks trains of action potential waveforms up to 200 Hz in single trials. With a favorable combination of brightness, dynamic range, and speed, ASAP1 enables continuous monitoring of membrane potential in neurons at KHz frame rates using standard epifluorescence microscopy. PMID:24755780

Stimulus waveform determines the characteristics of sensory nerve action potentials.

PubMed

Pereira, Pedro; Leote, João; Cabib, Christopher; Casanova-Molla, Jordi; Valls-Sole, Josep

2016-03-01

In routine nerve conduction studies supramaximal electrical stimuli generate sensory nerve action potentials by depolarization of nerve fibers under the cathode. However, stimuli of submaximal intensity may give rise to action potentials generated under the anode. We tested if this phenomenon depends on the characteristics of stimulus ending. We added a circuit to our stimulation device that allowed us to modify the end of the stimulus by increasing the time constant of the decay phase. Increasing the fall time caused a reduction of anode action potential (anAP) amplitude, and eventually abolished it, in all tested subjects. We subsequently examined the stimulus waveform in a series of available electromyographs stimulators and found that the anAP could only be obtained with stimulators that issued stimuli ending sharply. Our results prove that the anAP is generated at stimulus end, and depends on the sharpness of current shut down. Electromyographs produce stimuli of varying characteristics, which limits the reproducibility of anAP results by interested researchers. The study of anodal action potentials might be a useful tool to have a quick appraisal of distal human sensory nerve excitability. Copyright © 2015 International Federation of Clinical Neurophysiology. Published by Elsevier Ireland Ltd. All rights reserved.

Effects of Muscle Atrophy on Motor Control: Cage-size Effects

NASA Technical Reports Server (NTRS)

Stuart, D. G.

1985-01-01

Two populations of male Sprague-Dawley rats were raised either in conventional minimum-specification cages or in a larger cage. When the animals were mature (125 to 150 d), the physiological status of the soleus (SOL) and extensor digitorum longus (EDL) muscles of the small- and large-cage animals were compared. Analysis of whole-muscle properties including the performance of the test muscle during a standardized fatigue test in which the nerve to the test muscle was subjected to supramaximal intermittent stimulation shows: (1) the amplitude, area, mean amplitude, and peak-to-peak rate of the compound muscle action potential decreased per the course of the fatigue test; (2) cage size did not affect the profile of changes for any of the action-potential measurements; (3) changes exhibited in the compound muscle action potential by SOL and EDL were substantially different; and (4) except for SOL of the large-cage rats, there was a high correlation between all four measures of the compound muscle action potential and the peak tetanic force during the fatigue test; i.e., either the electrical activity largely etermines the force profile during the fatigue test or else contractile-related activity substantially affects the compound muscle action potential.

Electromyography (image)

MedlinePlus

... inserted through the skin into the muscle. Each muscle fiber that contracts will produce an action potential. The presence, size, and shape of the wave form of the action potential ... the ability of the muscle to respond to nervous stimulation.

Modeling the action-potential-sensitive nonlinear-optical response of myelinated nerve fibers and short-term memory

NASA Astrophysics Data System (ADS)

Shneider, M. N.; Voronin, A. A.; Zheltikov, A. M.

2011-11-01

The Goldman-Albus treatment of the action-potential dynamics is combined with a phenomenological description of molecular hyperpolarizabilities into a closed-form model of the action-potential-sensitive second-harmonic response of myelinated nerve fibers with nodes of Ranvier. This response is shown to be sensitive to nerve demyelination, thus enabling an optical diagnosis of various demyelinating diseases, including multiple sclerosis. The model is applied to examine the nonlinear-optical response of a three-neuron reverberating circuit—the basic element of short-term memory.

Position-dependent patterning of spontaneous action potentials in immature cochlear inner hair cells

PubMed Central

Johnson, Stuart L.; Eckrich, Tobias; Kuhn, Stephanie; Zampini, Valeria; Franz, Christoph; Ranatunga, Kishani M.; Roberts, Terri P.; Masetto, Sergio; Knipper, Marlies; Kros, Corné J.; Marcotti, Walter

2011-01-01

Spontaneous action potential activity is crucial for mammalian sensory system development. In the auditory system, patterned firing activity has been observed in immature spiral ganglion cells and brain-stem neurons and is likely to depend on cochlear inner hair cell (IHC) action potentials. It remains uncertain whether spiking activity is intrinsic to developing IHCs and whether it shows patterning. We found that action potentials are intrinsically generated by immature IHCs of altricial rodents and that apical IHCs exhibit bursting activity as opposed to more sustained firing in basal cells. We show that the efferent neurotransmitter ACh, by fine-tuning the IHC’s resting membrane potential (Vm), is crucial for the bursting pattern in apical cells. Endogenous extracellular ATP also contributes to the Vm of apical and basal IHCs by activating SK2 channels. We hypothesize that the difference in firing pattern along the cochlea instructs the tonotopic differentiation of IHCs and auditory pathway. PMID:21572434

Position-dependent patterning of spontaneous action potentials in immature cochlear inner hair cells.

PubMed

Johnson, Stuart L; Eckrich, Tobias; Kuhn, Stephanie; Zampini, Valeria; Franz, Christoph; Ranatunga, Kishani M; Roberts, Terri P; Masetto, Sergio; Knipper, Marlies; Kros, Corné J; Marcotti, Walter

2011-06-01

Spontaneous action potential activity is crucial for mammalian sensory system development. In the auditory system, patterned firing activity has been observed in immature spiral ganglion and brain-stem neurons and is likely to depend on cochlear inner hair cell (IHC) action potentials. It remains uncertain whether spiking activity is intrinsic to developing IHCs and whether it shows patterning. We found that action potentials were intrinsically generated by immature IHCs of altricial rodents and that apical IHCs showed bursting activity as opposed to more sustained firing in basal cells. We show that the efferent neurotransmitter acetylcholine fine-tunes the IHC's resting membrane potential (V(m)), and as such is crucial for the bursting pattern in apical cells. Endogenous extracellular ATP also contributes to the V(m) of apical and basal IHCs by triggering small-conductance Ca(2+)-activated K(+) (SK2) channels. We propose that the difference in firing pattern along the cochlea instructs the tonotopic differentiation of IHCs and auditory pathway.

Examination of a demyelinated fiber by action-potential-encoded second harmonic generation

NASA Astrophysics Data System (ADS)

Chen, Xin-guang; Luo, Zhi-hui; Yang, Hong-qin; Huang, Yi-mei; Xie, Shu-sen

2012-03-01

Axonal demyelination is a common phenomenon in the nervous system in human. Conventional measured approaches such as surface recording electrode and diffusion tensor imaging, are hard to fast and accurately determine the demyelinated status of a fiber. In this study, we first presented a mathematical model of nerve fiber demyelination, and it was combined with second harmonic generation(SHG) technique to study the characteristics of action-potential-encoded SHG and analyze the sensitivity of SHG signals responded to membrane potential. And then, we used this approach to fast examine the injured myelin sheaths resulted from demyelination. Each myelin sheath of a fiber was examined simultaneously by this approach. The results showed that fiber demyelination led to observable attenuation of action potential amplitude. The delay of action potential conduction would be markedly observed when the fiber demyelination was more than 80%. Furthermore, the normal and injured myelin sheaths of a myelinated fiber could be distinguished via the changes of SHG signals, which revealed the possibility of SHG technique in the examination of a demyelinated fiber. Our study shows that this approach may have potential application values in clinic.

Expeditionary Readiness Training (ExpeRT) Course Expansion Final Environmental Assessment Creech Air Force Base

DTIC Science & Technology

2006-07-01

potential environmental consequences of the proposed action and no-action alternative and are addressed for: air quality, soils and water resources...evaluated in detail to identify potential environmental consequences: air quality; soils and water resources; biological resources; and cultural resources...significance. Therefore, this proposed action would not constitute a significant impact and would conform to regional standards. Soils and Water Resources

Voltage-gated currents in identified rat olfactory receptor neurons.

PubMed

Trombley, P Q; Westbrook, G L

1991-02-01

Whole-cell recording techniques were used to characterize voltage-gated membrane currents in neonatal rat olfactory receptor neurons (ORNs) in cell culture. Mature ORNs were identified in culture by their characteristic bipolar morphology, by retrograde labeling techniques, and by olfactory marker protein (OMP) immunoreactivity. ORNs did not have spontaneous activity, but fired action potentials to depolarizing current pulses. Action potentials were blocked by tetrodotoxin (TTX), which contrasts with the TTX-resistant action potentials in salamander olfactory receptor cells (e.g., Firestein and Werblin, 1987). Prolonged, suprathreshold current pulses evoked only a single action potential; however, repetitive firing up to 35 Hz could be elicited by a series of brief depolarizing pulses. Under voltage clamp, the TTX-sensitive sodium current had activation and inactivation properties similar to other excitable cells. In TTX and 20 mM barium, sustained inward current were evoked by voltage steps positive to -30 mV. This current was blocked by Cd (100 microM) and by nifedipine (IC50 = 368 nM) consistent with L-type calcium channels in other neurons. No T-type calcium current was observed. Voltage steps positive to -20 mV also evoked an outward current that did not inactivate during 100-msec depolarizations. Tail current analysis of this current was consistent with a selective potassium conductance. The outward current was blocked by external tetraethylammonium but was unaffected by Cd or 4-aminopyridine (4-AP) or by removal of external calcium. A transient outward current was not observed. The 3 voltage-dependent conductances in cultured rat ORNs appear to be sufficient for 2 essential functions: action potential generation and transmitter release. As a single odorant-activated channel can trigger an action potential (e.g., Lynch and Barry, 1989), the repetitive firing seen with brief depolarizing pulses suggests that ORNs do not integrate sensory input, but rather act as high-fidelity relays such that each opening of an odorant-activated channel reaches the olfactory bulb glomeruli as an action potential.

The Potential of Deweyan-Inspired Action Research

ERIC Educational Resources Information Center

Stark, Jody L.

2014-01-01

In its broadest sense, pragmatism could be said to be the philosophical orientation of all action research. Action research is characterized by research, action, and participation grounded in democratic principles and guided by the aim of social improvement. Furthermore, action research is an active process of inquiry that does not admit…

Signal propagation along the axon.

PubMed

Rama, Sylvain; Zbili, Mickaël; Debanne, Dominique

2018-03-08

Axons link distant brain regions and are usually considered as simple transmission cables in which reliable propagation occurs once an action potential has been generated. Safe propagation of action potentials relies on specific ion channel expression at strategic points of the axon such as nodes of Ranvier or axonal branch points. However, while action potentials are generally considered as the quantum of neuronal information, their signaling is not entirely digital. In fact, both their shape and their conduction speed have been shown to be modulated by activity, leading to regulations of synaptic latency and synaptic strength. We report here newly identified mechanisms of (1) safe spike propagation along the axon, (2) compartmentalization of action potential shape in the axon, (3) analog modulation of spike-evoked synaptic transmission and (4) alteration in conduction time after persistent regulation of axon morphology in central neurons. We discuss the contribution of these regulations in information processing. Copyright © 2018 Elsevier Ltd. All rights reserved.

Action potentials drive body wall muscle contractions in Caenorhabditis elegans

PubMed Central

Gao, Shangbang; Zhen, Mei

2011-01-01

The sinusoidal locomotion exhibited by Caenorhabditis elegans predicts a tight regulation of contractions and relaxations of its body wall muscles. Vertebrate skeletal muscle contractions are driven by voltage-gated sodium channel–dependent action potentials. How coordinated motor outputs are regulated in C. elegans, which does not have voltage-gated sodium channels, remains unknown. Here, we show that C. elegans body wall muscles fire all-or-none, calcium-dependent action potentials that are driven by the L-type voltage-gated calcium and Kv1 voltage-dependent potassium channels. We further demonstrate that the excitatory and inhibitory motoneuron activities regulate the frequency of action potentials to coordinate muscle contraction and relaxation, respectively. This study provides direct evidence for the dual-modulatory model of the C. elegans motor circuit; moreover, it reveals a mode of motor control in which muscle cells integrate graded inputs of the nervous system and respond with all-or-none electrical signals. PMID:21248227

A Parametric Computational Model of the Action Potential of Pacemaker Cells.

PubMed

Ai, Weiwei; Patel, Nitish D; Roop, Partha S; Malik, Avinash; Andalam, Sidharta; Yip, Eugene; Allen, Nathan; Trew, Mark L

2018-01-01

A flexible, efficient, and verifiable pacemaker cell model is essential to the design of real-time virtual hearts that can be used for closed-loop validation of cardiac devices. A new parametric model of pacemaker action potential is developed to address this need. The action potential phases are modeled using hybrid automaton with one piecewise-linear continuous variable. The model can capture rate-dependent dynamics, such as action potential duration restitution, conduction velocity restitution, and overdrive suppression by incorporating nonlinear update functions. Simulated dynamics of the model compared well with previous models and clinical data. The results show that the parametric model can reproduce the electrophysiological dynamics of a variety of pacemaker cells, such as sinoatrial node, atrioventricular node, and the His-Purkinje system, under varying cardiac conditions. This is an important contribution toward closed-loop validation of cardiac devices using real-time heart models.

Initiation and blocking of the action potential in an axon in weak ultrasonic or microwave fields

NASA Astrophysics Data System (ADS)

Shneider, M. N.; Pekker, M.

2014-05-01

In this paper, we analyze the effect of the redistribution of the transmembrane ion channels in an axon caused by longitudinal acoustic vibrations of the membrane. These oscillations can be excited by an external source of ultrasound and weak microwave radiation interacting with the charges sitting on the surface of the lipid membrane. It is shown, using the Hodgkin-Huxley model of the axon, that the density redistribution of transmembrane sodium channels may reduce the threshold of the action potential, up to its spontaneous initiation. At the significant redistribution of sodium channels in the membrane, the rarefaction zones of the transmembrane channel density are formed, blocking the propagation of the action potential. Blocking the action potential propagation along the axon is shown to cause anesthesia in the example case of a squid axon. Various approaches to experimental observation of the effects considered in this paper are discussed.

Reliability of directional information in unsorted spikes and local field potentials recorded in human motor cortex.

PubMed

Perge, János A; Zhang, Shaomin; Malik, Wasim Q; Homer, Mark L; Cash, Sydney; Friehs, Gerhard; Eskandar, Emad N; Donoghue, John P; Hochberg, Leigh R

2014-08-01

Action potentials and local field potentials (LFPs) recorded in primary motor cortex contain information about the direction of movement. LFPs are assumed to be more robust to signal instabilities than action potentials, which makes LFPs, along with action potentials, a promising signal source for brain-computer interface applications. Still, relatively little research has directly compared the utility of LFPs to action potentials in decoding movement direction in human motor cortex. We conducted intracortical multi-electrode recordings in motor cortex of two persons (T2 and [S3]) as they performed a motor imagery task. We then compared the offline decoding performance of LFPs and spiking extracted from the same data recorded across a one-year period in each participant. We obtained offline prediction accuracy of movement direction and endpoint velocity in multiple LFP bands, with the best performance in the highest (200-400 Hz) LFP frequency band, presumably also containing low-pass filtered action potentials. Cross-frequency correlations of preferred directions and directional modulation index showed high similarity of directional information between action potential firing rates (spiking) and high frequency LFPs (70-400 Hz), and increasing disparity with lower frequency bands (0-7, 10-40 and 50-65 Hz). Spikes predicted the direction of intended movement more accurately than any individual LFP band, however combined decoding of all LFPs was statistically indistinguishable from spike-based performance. As the quality of spiking signals (i.e. signal amplitude) and the number of significantly modulated spiking units decreased, the offline decoding performance decreased 3.6[5.65]%/month (for T2 and [S3] respectively). The decrease in the number of significantly modulated LFP signals and their decoding accuracy followed a similar trend (2.4[2.85]%/month, ANCOVA, p = 0.27[0.03]). Field potentials provided comparable offline decoding performance to unsorted spikes. Thus, LFPs may provide useful external device control using current human intracortical recording technology. ( NCT00912041.).

Sodium and potassium conductance changes during a membrane action potential

PubMed Central

Bezanilla, Francisco; Rojas, Eduardo; Taylor, Robert E.

1970-01-01

1. A method for turning a membrane potential control system on and off in less than 10 μsec is described. This method was used to record membrane currents in perfused giant axons from Dosidicus gigas and Loligo forbesi after turning on the voltage clamp system at various times during the course of a membrane action potential. 2. The membrane current measured just after the capacity charging transient was found to have an almost linear relation to the controlled membrane potential. 3. The total membrane conductance taken from these current—voltage curves was found to have a time course during the action potential similar to that found by Cole & Curtis (1939). 4. The instantaneous current voltage curves were linear enough to make it possible to obtain a good estimate of the individual sodium and potassium channel conductances, either algebraically or by clamping to the sodium, or potassium, reversal potentials. Good general agreement was obtained with the predictions of the Hodgkin—Huxley equations. 5. We consider these results to constitute the first direct experimental demonstration of the conductance changes to sodium and potassium during the course of an action potential. PMID:5505231

GABAergic excitation of spider mechanoreceptors increases information capacity by increasing entropy rather than decreasing jitter.

PubMed

Pfeiffer, Keram; French, Andrew S

2009-09-02

Neurotransmitter chemicals excite or inhibit a range of sensory afferents and sensory pathways. These changes in firing rate or static sensitivity can also be associated with changes in dynamic sensitivity or membrane noise and thus action potential timing. We measured action potential firing produced by random mechanical stimulation of spider mechanoreceptor neurons during long-duration excitation by the GABAA agonist muscimol. Information capacity was estimated from signal-to-noise ratio by averaging responses to repeated identical stimulation sequences. Information capacity was also estimated from the coherence function between input and output signals. Entropy rate was estimated by a data compression algorithm and maximum entropy rate from the firing rate. Action potential timing variability, or jitter, was measured as normalized interspike interval distance. Muscimol increased firing rate, information capacity, and entropy rate, but jitter was unchanged. We compared these data with the effects of increasing firing rate by current injection. Our results indicate that the major increase in information capacity by neurotransmitter action arose from the increased entropy rate produced by increased firing rate, not from reduction in membrane noise and action potential jitter.

Mechanisms of action of ligands of potential-dependent sodium channels.

PubMed

Tikhonov, D B

2008-06-01

Potential-dependent sodium channels play a leading role in generating action potentials in excitable cells. Sodium channels are the site of action of a variety of modulator ligands. Despite numerous studies, the mechanisms of action of many modulators remain incompletely understood. The main reason that many important questions cannot be resolved is that there is a lack of precise data on the structures of the channels themselves. Structurally, potential-dependent sodium channels are members of the P-loop channel superfamily, which also include potassium and calcium channels and glutamate receptor channels. Crystallization of a series of potassium channels showed that it was possible to analyze the structures of different members of the superfamily using the "homologous modeling" method. The present study addresses model investigations of the actions of ligands of sodium channels, including tetrodotoxin and batrachotoxin, as well as local anesthetics. Comparison of experimental data on sodium channel ligands with x-ray analysis data allowed us to reach a new level of understanding of the mechanisms of channel modulation and to propose a series of experimentally verifiable hypotheses.

Rate dependency of delayed rectifier currents during the guinea-pig ventricular action potential

PubMed Central

Rocchetti, Marcella; Besana, Alessandra; Gurrola, Georgina B; Possani, Lourival D; Zaza, Antonio

2001-01-01

The action potential clamp technique was exploited to evaluate the rate dependency of delayed rectifier currents (IKr and IKs) during physiological electrical activity. IKr and IKs were measured in guinea-pig ventricular myocytes at pacing cycle lengths (CL) of 1000 and 250 ms.A shorter CL, with the attendant changes in action potential shape, was associated with earlier activation and increased magnitude of both IKr and IKs. Nonetheless, the relative contributions of IKr and IKs to total transmembrane current were independent of CL.Shortening of diastolic interval only (constant action potential shape) enhanced IKs, but not IKr.IKr was increased by a change in the action potential shape only (constant diastolic interval).In ramp clamp experiments, IKr amplitude was directly proportional to repolarization rate at values within the low physiological range (< 1.0 V s−1); at higher repolarization rates proportionality became shallower and finally reversed.When action potential duration (APD) was modulated by constant current injection (I-clamp), repolarization rates > 1.0 V s−1 were associated with a reduced effect of IKr block on APD. The effect of changes in repolarization rate was independent of CL and occurred in the presence of IKs blockade.In spite of its complexity, the behaviour of IKr was accurately predicted by a numerical model based entirely on known kinetic properties of the current.Both IKr and IKs may be increased at fast heart rates, but this may occur through completely different mechanisms. The mechanisms identified are such as to contribute to abnormal rate dependency of repolarization in prolonged repolarization syndromes. PMID:11483703

Electrophysiological, vasoactive, and gastromodulatory effects of stevia in healthy Wistar rats.

PubMed

Yesmine, Saquiba; Connolly, Kylie; Hill, Nicholas; Coulson, Fiona R; Fenning, Andrew S

2013-07-01

Antihypertensive and antidiabetic effects of stevia, Stevia rebaudiana (Asteraceae), have been demonstrated in several human and animal models. The current study aims to define stevia's role in modifying the electrophysiological and mechanical properties of cardiomyocytes, blood vessels, and gastrointestinal smooth muscle. Tissues from thoracic aorta, mesenteric arteries, ileum, and left ventricular papillary muscles were excised from 8-week-old healthy Wistar rats. The effects of stevia (1 × 10-9 M to 1 × 10-4 M) were measured on these tissues. Stevia's effects in the presence of verapamil, 4-AP, and L-NAME were also assessed. In cardiomyocytes, stevia attenuated the force of contraction, decreased the average peak amplitude, and shortened the repolarisation phase of action potential - repolarisation phase of action potential20 by 25 %, repolarisation phase of action potential50 by 34 %, and repolarisation phase of action potential90 by 36 %. Stevia caused relaxation of aortic tissues which was significantly potentiated in the presence of verapamil. In mesenteric arteries, incubation with L-NAME failed to block stevia-induced relaxation indicating the mechanism of action may not be fully via nitric oxide-dependent pathways. Stevia concentration-dependently reduced electrical field stimulated and carbachol-induced contractions in the isolated ileum. This study is the first to show the effectiveness of stevia in reducing cardiac action potential duration at 20 %, 50 %, and 90 % of repolarisation. Stevia also showed beneficial modulatory effects on cardiovascular and gastrointestinal tissues via calcium channel antagonism, activation of the M2 muscarinic receptor function, and enhanced nitric oxide release. Georg Thieme Verlag KG Stuttgart · New York.

Rosewood oil induces sedation and inhibits compound action potential in rodents.

PubMed

de Almeida, Reinaldo Nóbrega; Araújo, Demétrius Antonio Machado; Gonçalves, Juan Carlos Ramos; Montenegro, Fabrícia Costa; de Sousa, Damião Pergentino; Leite, José Roberto; Mattei, Rita; Benedito, Marco Antonio Campana; de Carvalho, José Gilberto Barbosa; Cruz, Jader Santos; Maia, José Guilherme Soares

2009-07-30

Aniba rosaeodora is an aromatic plant which has been used in Brazil folk medicine due to its sedative effect. Therefore, the purpose of the present study was to evaluate the sedative effect of linalool-rich rosewood oil in mice. In addition we sought to investigate the linalool-rich oil effects on the isolated nerve using the single sucrose-gap technique. Sedative effect was determined by measuring the potentiation of the pentobarbital-induced sleeping time. The compound action potential amplitude was evaluated as a way to detect changes in excitability of the isolated nerve. The results showed that administration of rosewood oil at the doses of 200 and 300 mg/kg significantly decreased latency and increased the duration of sleeping time. On the other hand, the dose of 100 mg/kg potentiated significantly the pentobarbital action decreasing pentobarbital latency time and increasing pentobarbital sleeping time. In addition, the effect of linalool-rich rosewood oil on the isolated nerve of the rat was also investigated through the single sucrose-gap technique. The amplitude of the action potential decreased almost 100% when it was incubated for 30 min at 100 microg/ml. From this study, it is suggested a sedative effect of linalool-rich rosewood oil that could, at least in part, be explained by the reduction in action potential amplitude that provokes a decrease in neuronal excitability.

Outcome producing potential influences twelve-month-olds' interpretation of a novel action as goal-directed.

PubMed

Biro, Szilvia; Verschoor, Stephan; Coalter, Esther; Leslie, Alan M

2014-11-01

Learning about a novel, goal-directed action is a complex process. It requires identifying the outcome of the action and linking the action to its outcome for later use in new situations to predict the action or to anticipate its outcome. We investigated the hypothesis that linking a novel action to a salient change in the environment is critical for infants to assign a goal to the novel action. We report a study in which we show that 12-month-old infants, who were provided with prior experience with a novel action accompanied with a salient visible outcome in one context, can interpret the same action as goal-directed even in the absence of the outcome in another context. Our control condition shows that prior experience with the action, but without the salient effect, does not lead to goal-directed interpretation of the novel action. We also found that, for the case of 9-month-olds infants, prior experience with the outcome producing potential of the novel action does not facilitate a goal-directed interpretation of the action. However, this failure was possibly due to difficulties with generalizing the learnt association to another context rather than with linking the action to its outcome. Copyright © 2014 Elsevier Inc. All rights reserved.

Critical Action Research and Third Wave Feminism: A Meeting of Paradigms

ERIC Educational Resources Information Center

Weiner, Gaby

2004-01-01

Critical action research emphasises participation, democracy and social critique, and thus has had considerable potential for feminist scholarship and action. Feminist action research, in turn, has gained a foothold in education, for example, through the work of Hollingsworth, Miller, Lather and others, although much action research might still be…

Enhancing Postgraduate Learning and Development: A Participatory Action Learning and Action Research Approach through Conferences

ERIC Educational Resources Information Center

Wood, Lesley; Louw, Ina; Zuber-Skerritt, Ortrun

2017-01-01

As supervisors who advocate the transformational potential of research both to generate theory and practical and emancipatory outcomes, we practice participatory action learning and action research (PALAR). This paper offers an illustrative case of how supervision practices based on action learning can foster emancipatory and lifelong learning…

SL(2, C) group action on cohomological field theories

NASA Astrophysics Data System (ADS)

Basalaev, Alexey

2018-01-01

We introduce the S} (2,C) group action on a partition function of a cohomological field theory via a certain Givental's action. Restricted to the small phase space we describe the action via the explicit formulae on a CohFT genus g potential. We prove that applied to the total ancestor potential of a simple-elliptic singularity the action introduced coincides with the transformation of Milanov-Ruan changing the primitive form (cf. Milanov and Ruan in Gromov-Witten theory of elliptic orbifold P1 and quasi-modular forms, arXiv:1106.2321 , 2011).

Assessing potentially dangerous medical actions with the computer-based case simulation portion of the USMLE step 3 examination.

PubMed

Harik, Polina; Cuddy, Monica M; O'Donovan, Seosaimhin; Murray, Constance T; Swanson, David B; Clauser, Brian E

2009-10-01

The 2000 Institute of Medicine report on patient safety brought renewed attention to the issue of preventable medical errors, and subsequently specialty boards and the National Board of Medical Examiners were encouraged to play a role in setting expectations around safety education. This paper examines potentially dangerous actions taken by examinees during the portion of the United States Medical Licensing Examination Step 3 that is particularly well suited to evaluating lapses in physician decision making, the Computer-based Case Simulation (CCS). Descriptive statistics and a general linear modeling approach were used to analyze dangerous actions ordered by 25,283 examinees that completed CCS for the first time between November 2006 and January 2008. More than 20% of examinees ordered at least one dangerous action with the potential to cause significant patient harm. The propensity to order dangerous actions may vary across clinical cases. The CCS format may provide a means of collecting important information about patient-care situations in which examinees may be more likely to commit dangerous actions and the propensity of examinees to order dangerous tests and treatments.

Crataegus extract prolongs action potential duration in guinea-pig papillary muscle.

PubMed

Müller, A; Linke, W; Zhao, Y; Klaus, W

1996-11-01

Crataegus extract is used in cardiology for the treatment of moderate heart failure (NYHA II). Recently it was shown that Crataegus extract prolongs the refractory period in isolated perfused guinea pig hearts. In order to find out what mechanism is responsible for this prolongation of refractory period, we investigated the effects of Crataegus extract (LI 132) on the action potential of guinea pig papillary muscle with the help of conventional microelectrode techniques. Crataegus extract, when put in a concentration (10 mg/l) capable of inducing an inotropic effect of about 20%, significantly increased action potential duration at all investigated levels of repolarisation. Maximum prolongation was 8.5±2.3 ms, 12.5±2.6 ms and 11.7±2.9 ms at 20%, 50% and 90% repolarisation, respectively (control APD(90): 172±4 ms). Experiments on the time course of recovery of the maximum upstroke velocity (V(max)) of the action potential revealed that Crataegus extract increased the time constant of recovery of V(max) from 8.80±2.33 ms to 22.60±5.77 ms, indicating a weak Class I-like antiarrhythmic action. In addition, we observed a small reduction in V(max). In summary, our results show that Crataegus extract prolongs action potential duration and delays recovery of V(max). We, therefore, suggest that Crataegus extract possesses certain antiarrhythmic properties. Copyright © 1996 Gustav Fischer Verlag · Stuttgart · Jena · New York. Published by Elsevier GmbH.. All rights reserved.

Modeling specific action potentials in the human atria based on a minimal single-cell model.

PubMed

Richter, Yvonne; Lind, Pedro G; Maass, Philipp

2018-01-01

We present an effective method to model empirical action potentials of specific patients in the human atria based on the minimal model of Bueno-Orovio, Cherry and Fenton adapted to atrial electrophysiology. In this model, three ionic are currents introduced, where each of it is governed by a characteristic time scale. By applying a nonlinear optimization procedure, a best combination of the respective time scales is determined, which allows one to reproduce specific action potentials with a given amplitude, width and shape. Possible applications for supporting clinical diagnosis are pointed out.

Reconstruction of the action potential of ventricular myocardial fibres

PubMed Central

Beeler, G. W.; Reuter, H.

1977-01-01

1. A mathematical model of membrane action potentials of mammalian ventricular myocardial fibres is described. The reconstruction model is based as closely as possible on ionic currents which have been measured by the voltage-clamp method. 2. Four individual components of ionic current were formulated mathematically in terms of Hodgkin—Huxley type equations. The model incorporates two voltage- and time-dependent inward currents, the excitatory inward sodium current, iNa, and a secondary or slow inward current, is, primarily carried by calcium ions. A time-independent outward potassium current, iK1, exhibiting inward-going rectification, and a voltage- and time-dependent outward current, ix1, primarily carried by potassium ions, are further elements of the model. 3. The iNa is primarily responsible for the rapid upstroke of the action potential, while the other current components determine the configuration of the plateau of the action potential and the re-polarization phase. The relative importance of inactivation of is and of activation of ix1 for termination of the plateau is evaluated by the model. 4. Experimental phenomena like slow recovery of the sodium system from inactivation, frequency dependence of the action potential duration, all-or-nothing re-polarization, membrane oscillations are adequately described by the model. 5. Possible inadequacies and shortcomings of the model are discussed. PMID:874889

Novel design of electrical sensing interface for prosthetic limbs using optical micro cavities

NASA Astrophysics Data System (ADS)

Ali, Amir R.; Kamel, Mohamed A.

2018-04-01

This paper uses optical whispering galley modes (WGM) cavities to construct a new electrical sensing interface between prosthetic limb and the brain. The sensing element will detect the action potential signal in the neural membrane and the prosthetic limb will be actuated accordingly. The element is a WGM dielectric polymeric cavity. WGM based optical cavities can achieve very high values of sensitivity and quality factor; thus, any minute perturbations in the morphology of the cavity can be captured and measured. The action potential signal will produce an applied external electric field on the dielectric cavity causing it to deform due to the electrostriction effect. The resulting deformation will cause WGM shifts in the transmission spectrum of the cavity. Thus, the action potential or the applied electric field can be measured using these shifts. In this paper the action potential signal will be simulated through the use of a function generator and two metal electrodes. The sensing element will be situated between these electrodes to detect the electrical signal passing through. The achieved sensitivity is 27.5 pm/V in measuring the simulated action potential signal; and 0.32 pm/V.m-1 in measuring the applied electric field due to the passage of the simulated signal.

Potentiation of substance p by lysergic acid diethylamide in vivo

PubMed Central

Krivoy, W. A.

1961-01-01

In doses of 10 μg/kg or more, lysergic acid diethylamide enhanced the fourth potential (DR IV) of the dorsal root potential complex in the cat. Smaller doses of lysergic acid diethylamide did not in themselves alter the DR IV, but revealed an enhancement of the potential by substance P, which by itself had no effect. 2-Bromolysergic acid diethylamide had no action on the dorsal root potentials, but prevented the actions of lysergic acid diethylamide. PMID:13754427

Activation of Mechanosensitive Transient Receptor Potential/Piezo Channels in Odontoblasts Generates Action Potentials in Cocultured Isolectin B4-negative Medium-sized Trigeminal Ganglion Neurons.

PubMed

Sato, Masaki; Ogura, Kazuhiro; Kimura, Maki; Nishi, Koichi; Ando, Masayuki; Tazaki, Masakazu; Shibukawa, Yoshiyuki

2018-06-01

Various stimuli to the dentin surface elicit dentinal pain by inducing dentinal fluid movement causing cellular deformation in odontoblasts. Although odontoblasts detect deformation by the activation of mechanosensitive ionic channels, it is still unclear whether odontoblasts are capable of establishing neurotransmission with myelinated A delta (Aδ) neurons. Additionally, it is still unclear whether these neurons evoke action potentials by neurotransmitters from odontoblasts to mediate sensory transduction in dentin. Thus, we investigated evoked inward currents and evoked action potentials form trigeminal ganglion (TG) neurons after odontoblast mechanical stimulation. We used patch clamp recordings to identify electrophysiological properties and record evoked responses in TG neurons. We classified TG cells into small-sized and medium-sized neurons. In both types of neurons, we observed voltage-dependent inward currents. The currents from medium-sized neurons showed fast inactivation kinetics. When mechanical stimuli were applied to odontoblasts, evoked inward currents were recorded from medium-sized neurons. Antagonists for the ionotropic adenosine triphosphate receptor (P2X 3 ), transient receptor potential channel subfamilies, and Piezo1 channel significantly inhibited these inward currents. Mechanical stimulation to odontoblasts also generated action potentials in the isolectin B 4 -negative medium-sized neurons. Action potentials in these isolectin B 4 -negative medium-sized neurons showed a short duration. Overall, electrophysiological properties of neurons indicate that the TG neurons with recorded evoked responses after odontoblast mechanical stimulation were myelinated Aδ neurons. Odontoblasts established neurotransmission with myelinated Aδ neurons via P2X 3 receptor activation. The results also indicated that mechanosensitive TRP/Piezo1 channels were functionally expressed in odontoblasts. The activation of P2X 3 receptors induced an action potential in the Aδ neurons, underlying a sensory generation mechanism of dentinal pain. Copyright © 2018 American Association of Endodontists. Published by Elsevier Inc. All rights reserved.

Dynamic Action Potential Restitution Contributes to Mechanical Restitution in Right Ventricular Myocytes From Pulmonary Hypertensive Rats.

PubMed

Hardy, Matthew E L; Pervolaraki, Eleftheria; Bernus, Olivier; White, Ed

2018-01-01

We investigated the steepened dynamic action potential duration (APD) restitution of rats with pulmonary artery hypertension (PAH) and right ventricular (RV) failure and tested whether the observed APD restitution properties were responsible for negative mechanical restitution in these myocytes. PAH and RV failure were provoked in male Wistar rats by a single injection of monocrotaline (MCT) and compared with saline-injected animals (CON). Action potentials were recorded from isolated RV myocytes at stimulation frequencies between 1 and 9 Hz. Action potential waveforms recorded at 1 Hz were used as voltage clamp profiles (action potential clamp) at stimulation frequencies between 1 and 7 Hz to evoke rate-dependent currents. Voltage clamp profiles mimicking typical CON and MCT APD restitution were applied and cell shortening simultaneously monitored. Compared with CON myocytes, MCT myocytes were hypertrophied; had less polarized diastolic membrane potentials; had action potentials that were triggered by decreased positive current density and shortened by decreased negative current density; APD was longer and APD restitution steeper. APD90 restitution was unchanged by exposure to the late Na + -channel blocker (5 μM) ranolazine or the intracellular Ca 2+ buffer BAPTA. Under AP clamp, stimulation frequency-dependent inward currents were smaller in MCT myocytes and were abolished by BAPTA. In MCT myocytes, increasing stimulation frequency decreased contraction amplitude when depolarization duration was shortened, to mimic APD restitution, but not when depolarization duration was maintained. We present new evidence that the membrane potential of PAH myocytes is less stable than normal myocytes, being more easily perturbed by external currents. These observations can explain increased susceptibility to arrhythmias. We also present novel evidence that negative APD restitution is at least in part responsible for the negative mechanical restitution in PAH myocytes. Thus, our study links electrical restitution remodeling to a defining mechanical characteristic of heart failure, the reduced ability to respond to an increase in demand.

Action prediction based on anticipatory brain potentials during simulated driving.

PubMed

Khaliliardali, Zahra; Chavarriaga, Ricardo; Gheorghe, Lucian Andrei; Millán, José del R

2015-12-01

The ability of an automobile to infer the driver's upcoming actions directly from neural signals could enrich the interaction of the car with its driver. Intelligent vehicles fitted with an on-board brain-computer interface able to decode the driver's intentions can use this information to improve the driving experience. In this study we investigate the neural signatures of anticipation of specific actions, namely braking and accelerating. We investigated anticipatory slow cortical potentials in electroencephalogram recorded from 18 healthy participants in a driving simulator using a variant of the contingent negative variation (CNV) paradigm with Go and No-go conditions: count-down numbers followed by 'Start'/'Stop' cue. We report decoding performance before the action onset using a quadratic discriminant analysis classifier based on temporal features. (i) Despite the visual and driving related cognitive distractions, we show the presence of anticipatory event related potentials locked to the stimuli onset similar to the widely reported CNV signal (with an average peak value of -8 μV at electrode Cz). (ii) We demonstrate the discrimination between cases requiring to perform an action upon imperative subsequent stimulus (Go condition, e.g. a 'Red' traffic light) versus events that do not require such action (No-go condition; e.g. a 'Yellow' light); with an average single trial classification performance of 0.83 ± 0.13 for braking and 0.79 ± 0.12 for accelerating (area under the curve). (iii) We show that the centro-medial anticipatory potentials are observed as early as 320 ± 200 ms before the action with a detection rate of 0.77 ± 0.12 in offline analysis. We show for the first time the feasibility of predicting the driver's intention through decoding anticipatory related potentials during simulated car driving with high recognition rates.

Block of voltage-gated potassium channels by Pacific ciguatoxin-1 contributes to increased neuronal excitability in rat sensory neurons

DOE Office of Scientific and Technical Information (OSTI.GOV)

Birinyi-Strachan, Liesl C.; Gunning, Simon J.; Lewis, Richard J.

2005-04-15

The present study investigated the actions of the polyether marine toxin Pacific ciguatoxin-1 (P-CTX-1) on neuronal excitability in rat dorsal root ganglion (DRG) neurons using patch-clamp recording techniques. Under current-clamp conditions, bath application of 2-20 nM P-CTX-1 caused a rapid, concentration-dependent depolarization of the resting membrane potential in neurons expressing tetrodotoxin (TTX)-sensitive voltage-gated sodium (Na{sub v}) channels. This action was completely suppressed by the addition of 200 nM TTX to the external solution, indicating that this effect was mediated through TTX-sensitive Na{sub v} channels. In addition, P-CTX-1 also prolonged action potential and afterhyperpolarization (AHP) duration. In a subpopulation of neurons,more » P-CTX-1 also produced tonic action potential firing, an effect that was not accompanied by significant oscillation of the resting membrane potential. Conversely, in neurons expressing TTX-resistant Na{sub v} currents, P-CTX-1 failed to alter any parameter of neuronal excitability examined in this study. Under voltage-clamp conditions in rat DRG neurons, P-CTX-1 inhibited both delayed-rectifier and 'A-type' potassium currents in a dose-dependent manner, actions that occurred in the absence of alterations to the voltage dependence of activation. These actions appear to underlie the prolongation of the action potential and AHP, and contribute to repetitive firing. These data indicate that a block of potassium channels contributes to the increase in neuronal excitability, associated with a modulation of Na{sub v} channel gating, observed clinically in response to ciguatera poisoning.« less

Dual formulation of covariant nonlinear duality-symmetric action of kappa-symmetric D3-brane

NASA Astrophysics Data System (ADS)

Vanichchapongjaroen, Pichet

2018-02-01

We study the construction of covariant nonlinear duality-symmetric actions in dual formulation. Essentially, the construction is the PST-covariantisation and nonlinearisation of Zwanziger action. The covariantisation made use of three auxiliary scalar fields. Apart from these, the construction proceed in a similar way to that of the standard formulation. For example, the theories can be extended to include interactions with external fields, and that the theories possess two local PST symmetries. We then explicitly demonstrate the construction of covariant nonlinear duality-symmetric actions in dual formulation of DBI theory, and D3-brane. For each of these theories, the twisted selfduality condition obtained from duality-symmetric actions are explicitly shown to match with the duality relation between field strength and its dual from the one-potential actions. Their on-shell actions between the duality-symmetric and the one-potential versions are also shown to match. We also explicitly prove kappa-symmetry of the covariant nonlinear duality-symmetric D3-brane action in dual formulation.

Responses to Gamma-Aminobutyric Acid of Rat Visual Cortical Neurons in Tissue Slices

DTIC Science & Technology

1986-04-01

depolarizing afterpotentials ( DAPs ; Figure 3). The afterhyperpolarization (AHP) was defined as the hyperpolarization that follow one or more orthodromic...action potentials or action potentials elicited during a depolarizing current pulse (Figure 3). DAPs and AHPs were measured from the RMP. The term...inhibitory postsynaptic potential, DAP = depolarizing afterpotential, AHP= afterhyperpolarization. Dashed lines indicate the RMP. Asterisks indicate

A Self-Study of the Teaching of Action Research in a University Context

ERIC Educational Resources Information Center

Choi, Jung-ah

2011-01-01

Despite the potential benefits of action research, teaching action research in a university setting can present challenges. Analyzing my own experiences of teaching a university-based course on action research, this self-study investigates what my students (all classroom teachers) did and did not understand about action research and what hindered…

Mechanoelectric feedback in a model of the passively inflated left ventricle.

PubMed

Vetter, F J; McCulloch, A D

2001-05-01

Mechanoelectric feedback has been described in isolated cells and intact ventricular myocardium, but the mechanical stimulus that governs mechanosensitive channel activity in intact tissue is unknown. To study the interaction of myocardial mechanics and electrophysiology in multiple dimensions, we used a finite element model of the rabbit ventricles to simulate electrical propagation through passively loaded myocardium. Electrical propagation was simulated using the collocation-Galerkin finite element method. A stretch-dependent current was added in parallel to the ionic currents in the Beeler-Reuter ventricular action potential model. We investigated different mechanical coupling parameters to simulate stretch-dependent conductance modulated by either fiber strain, cross-fiber strain, or a combination of the two. In response to pressure loading, the conductance model governed by fiber strain alone reproduced the epicardial decrease in action potential amplitude as observed in experimental preparations of the passively loaded rabbit heart. The model governed by only cross-fiber strain reproduced the transmural gradient in action potential amplitude as observed in working canine heart experiments, but failed to predict a sufficient decrease in amplitude at the epicardium. Only the model governed by both fiber and cross-fiber strain reproduced the epicardial and transmural changes in action potential amplitude similar to experimental observations. In addition, dispersion of action potential duration nearly doubled with the same model. These results suggest that changes in action potential characteristics may be due not only to length changes along the long axis direction of the myofiber, but also due to deformation in the plane transverse to the fiber axis. The model provides a framework for investigating how cellular biophysics affect the function of the intact ventricles.

Effects of phloretin and phloridzin on Ca2+ handling, the action potential, and ion currents in rat ventricular myocytes.

PubMed

Olson, Marnie L; Kargacin, Margaret E; Ward, Christopher A; Kargacin, Gary J

2007-06-01

The effects of the phytoestrogens phloretin and phloridzin on Ca(2+) handling, cell shortening, the action potential, and Ca(2+) and K(+) currents in freshly isolated cardiac myocytes from rat ventricle were examined. Phloretin increased the amplitude and area and decreased the rate of decline of electrically evoked Ca(2+) transients in the myocytes. These effects were accompanied by an increase in the Ca(2+) load of the sarcoplasmic reticulum, as determined by the area of caffeine-evoked Ca(2+) transients. An increase in the extent of shortening of the myocytes in response to electrically evoked action potentials was also observed in the presence of phloretin. To further examine possible mechanisms contributing to the observed changes in Ca(2+) handling and contractility, the effects of phloretin on the cardiac action potential and plasma membrane Ca(2+) and K(+) currents were examined. Phloretin markedly increased the action potential duration in the myocytes, and it inhibited the Ca(2+)-independent transient outward K(+) current (I(to)). The inwardly rectifying K(+) current, the sustained outward delayed rectifier K(+) current, and L-type Ca(2+) currents were not significantly different in the presence and absence of phloretin, nor was there any evidence that the Na(+)/Ca(2+) exchanger was affected. The effects of phloretin on Ca(2+) handling in the myocytes are consistent with its effects on I(to). Phloridzin did not significantly alter the amplitude or area of electrically evoked Ca(2+) transients in the myocytes, nor did it have detectable effects on the sarcoplasmic reticulum Ca(2+) load, cell shortening, or the action potential.

Spatial variability in T-tubule and electrical remodeling of left ventricular epicardium in mouse hearts with transgenic Gαq overexpression-induced pathological hypertrophy

PubMed Central

Tao, Wen; Shi, Jianjian; Dorn, Gerald W.; Wei, Lei; Rubart, Michael

2012-01-01

Pathological left ventricular hypertrophy (LVH) is consistently associated with prolongation of the ventricular action potentials. A number of previous studies, employing various experimental models of hypertrophy, have revealed marked differences in the effects of hypertrophy on action potential duration (APD) between myocytes from endocardial and epicardial layers of the LV free wall. It is not known, however, whether pathological LVH is also accompanied by redistribution of APD among myocytes from the same layer in the LV free wall. In the experiments here, LV epicardial action potential remodeling was examined in a mouse model of decompensated LVH, produced by cardiac-restricted transgenic Gαq overexpression. Confocal linescanning-based optical recordings of propagated action potentials from individual in situ cardiomyocytes across the outer layer of the anterior LV epicardium demonstrated spatially non-uniform action potential prolongation in transgenic hearts, giving rise to alterations in spatial dispersion of epicardial repolarization. Local density and distribution of anti-Cx43 mmune reactivity in Gαq hearts were unchanged compared to wild-type hearts, suggesting preservation of intercellular coupling. Confocal microscopy also revealed heterogeneous disorganization of T-tubules in epicardial cardiomyocytes in situ. These data provide evidence of the existence of significant electrical and structural heterogeneity within the LV epicardial layer of hearts with transgenic Gαq overexpression-induced hypertrophy, and further support the notion that a small portion of electrically well connected LV tissue can maintain dispersion of action potential duration through heterogeneity in the activities of sarcolemmal ionic currents that control repolarization. It remains to be examined whether other experimental models of pathological LVH, including pressure overload LVH, similarly exhibit alterations in T-tubule organization and/or dispersion of repolarization within distinct layers of LV myocardium. PMID:22728217

Generalized alternating stimulation: a novel method to reduce stimulus artifact in electrically evoked compound action potentials.

PubMed

Alvarez, Isaac; de la Torre, Angel; Sainz, Manuel; Roldan, Cristina; Schoesser, Hansjoerg; Spitzer, Philipp

2007-09-15

Stimulus artifact is one of the main limitations when considering electrically evoked compound action potential for clinical applications. Alternating stimulation (average of recordings obtained with anodic-cathodic and cathodic-anodic bipolar stimulation pulses) is an effective method to reduce stimulus artifact when evoked potentials are recorded. In this paper we extend the concept of alternating stimulation by combining anodic-cathodic and cathodic-anodic recordings with a weight in general different to 0.5. We also provide an automatic method to obtain an estimation of the optimal weights. Comparison with conventional alternating, triphasic stimulation and masker-probe paradigm shows that the generalized alternating method improves the quality of electrically evoked compound action potential responses.

Low-energy effective action in two-dimensional SQED: a two-loop analysis

NASA Astrophysics Data System (ADS)

Samsonov, I. B.

2017-07-01

We study two-loop quantum corrections to the low-energy effective actions in N=(2,2) and N=(4,4) SQED on the Coulomb branch. In the latter model, the low-energy effective action is described by a generalized Kähler potential which depends on both chiral and twisted chiral superfields. We demonstrate that this generalized Kähler potential is one-loop exact and corresponds to the N=(4,4) sigma-model with torsion presented by Roček, Schoutens and Sevrin [1]. In the N=(2,2) SQED, the effective Kähler potential is not protected against higher-loop quantum corrections. The two-loop quantum corrections to this potential and the corresponding sigma-model metric are explicitly found.

Update on the mechanism of action of antiepileptic drugs.

PubMed

Meldrum, B S

1996-01-01

Novel antiepileptic drugs (AEDs) are thought to act on voltage-sensitive ion channels, on inhibitory neurotransmission or on excitatory neurotransmission. Two successful examples of rational AED design that potentiate GABA-mediated inhibition are vigabatrin (VGB) by irreversible inhibition of GABA-transaminase, and tiagabine (TGB) by blocking GABA uptake. Lamotrigine (LTG) prolongs inactivation of voltage-dependent sodium channels. The anticonvulsant action of remacemide (RCM) is probably largely due to blockade of NMDA receptors and prolonged inactivation of sodium channels induced by its desglycinated metabolite. Felbamate (FBM) apparently blocks NMDA receptors, potentiates GABA-mediated responses, blocks L-type calcium channels, and possibly also prolongs sodium channel inactivation. Similarly, topiramate (TPM) has multiple probable sites of action, including sodium channels, GABA receptors, and glutamate (AMPA) receptors. Gabapentin (GBP) apparently has a completely novel type of action, probably involving potentiation of GABA-mediated inhibition and possibly also inactivation of sodium channels. The therapeutic advantages of the novel AEDs are as yet only partially explained by our present understanding of their mechanisms of action.

Triple stimulation technique in patients with spinocerebellar ataxia type 6.

PubMed

Sakuma, Kenji; Adachi, Yoshiki; Fukuda, Hiroki; Kai, Tohru; Nakashima, Kenji

2005-11-01

To establish further evidence that SCA6 may not be a pure cerebellar syndrome. Seven patients with genetically confirmed SCA6 and 9 age-matched normal controls were studied. Recordings of the CMAP were obtained from the right first dorsal interosseus muscle. Transcranial magnetic stimulation of the left motor cortex was applied to the contralateral scalp with a plane figure-of-8 coil. Conventional transcranial magnetic stimulation (TMS), central motor conduction time (CMCT) by F-wave method and the triple stimulation technique (TST) amplitude ratio (TST test/TST control) were investigated. The mean resting motor threshold and mean CMCT did not show significant differences between normal controls and patients, but the mean TST amplitude ratio was significantly smaller in patients than in controls. An abnormal TST represents upper motor neuron loss, central axon lesions or conduction blocks, or inexcitability in response to TMS. The lack of pathological changes in the corticospinal tract of patients with SCA6 indicates that this abnormality may be caused by crossed cerebellar diaschisis, or a functional disorder in the brain resulting from CACNA1A mutations. TST is a useful method for quantifying corticospinal tract dysfunction.

Evaluation of RNAi and CRISPR technologies by large-scale gene expression profiling in the Connectivity Map.

PubMed

Smith, Ian; Greenside, Peyton G; Natoli, Ted; Lahr, David L; Wadden, David; Tirosh, Itay; Narayan, Rajiv; Root, David E; Golub, Todd R; Subramanian, Aravind; Doench, John G

2017-11-01

The application of RNA interference (RNAi) to mammalian cells has provided the means to perform phenotypic screens to determine the functions of genes. Although RNAi has revolutionized loss-of-function genetic experiments, it has been difficult to systematically assess the prevalence and consequences of off-target effects. The Connectivity Map (CMAP) represents an unprecedented resource to study the gene expression consequences of expressing short hairpin RNAs (shRNAs). Analysis of signatures for over 13,000 shRNAs applied in 9 cell lines revealed that microRNA (miRNA)-like off-target effects of RNAi are far stronger and more pervasive than generally appreciated. We show that mitigating off-target effects is feasible in these datasets via computational methodologies to produce a consensus gene signature (CGS). In addition, we compared RNAi technology to clustered regularly interspaced short palindromic repeat (CRISPR)-based knockout by analysis of 373 single guide RNAs (sgRNAs) in 6 cells lines and show that the on-target efficacies are comparable, but CRISPR technology is far less susceptible to systematic off-target effects. These results will help guide the proper use and analysis of loss-of-function reagents for the determination of gene function.

Investigating the Sensitivity of Model Intraseasonal Variability to Minimum Entrainment

NASA Astrophysics Data System (ADS)

Hannah, W. M.; Maloney, E. D.

2008-12-01

Previous studies have shown that using a Relaxed Arakawa-Schubert (RAS) convective parameterization with appropriate convective triggers and assumptions about rain re-evaporation produces realistic intraseasonal variability. RAS represents convection with an ensemble of clouds detraining at different heights, each with different entrainment rate, the highest clouds having the lowest entrainment rates. If tropospheric temperature gradients are weak and boundary layer moist static energy is relatively constant, then by limiting the minimum entrainment rate deep convection is suppressed in the presence of dry tropospheric air. This allows moist static energy to accumulate and be discharged during strong intraseasonal convective events, which is consistent with the discharge/recharge paradigm. This study will examine the sensitivity of intra-seasonal variability to changes in minimum entrainment rate in the NCAR-CAM3 with the RAS scheme. Simulations using several minimum entrainment rate thresholds will be investigated. A frequency-wavenumber analysis will show the improvement of the MJO signal as minimum entrainment rate is increased. The spatial and vertical structure of MJO-like disturbances will be examined, including an analysis of the time evolution of vertical humidity distribution for each simulation. Simulated results will be compared to observed MJO events in NCEP-1 reanalysis and CMAP precipitation.

Elastic resistance change and action potential generation of non-faradaic Pt/TiO2/Pt capacitors.

PubMed

Lim, Hyungkwang; Jang, Ho Won; Lee, Doh-Kwon; Kim, Inho; Hwang, Cheol Seong; Jeong, Doo Seok

2013-07-21

Electric current in the mixed ionic-electronic conductor TiO2 is hysteretic, i.e. history-dependent, and its use is versatile in electronic devices. Nowadays, biologically inspired, analogue-type computing systems, known as neuromorphic systems, are being actively investigated owing to their new and intriguing physical concepts. The realization of artificial synapses is important for constructing neuromorphic systems. In mammalians' brains, the plasticity of synapses between neighbouring nerve cells arises from action potential firing. Emulating action potential firing via inorganic systems has therefore become important in neuromorphic engineering. In this work, the current-voltage hysteresis of TiO2-based non-faradaic capacitors is investigated to primarily focus on the correlation between the blocking contact and the elasticity, i.e. non-plasticity, of the capacitors' resistance change, in experimental and theoretical methods. The similarity between the action potential firing behaviour in nerve cells and the elasticity of the non-faradaic capacitors is addressed.

Effects of boundaries and geometry on the spatial distribution of action potential duration in cardiac tissue

PubMed Central

Cherry, Elizabeth M.; Fenton, Flavio H.

2011-01-01

Increased dispersion of action potential duration across cardiac tissue has long been considered an important substrate for the development of most electrical arrhythmias. Although this dispersion has been studied previously by characterizing the static intrinsic gradients in cellular electrophysiology and dynamical gradients generated by fast pacing, few studies have concentrated on dispersions generated solely by structural effects. Here we show how boundaries and geometry can produce spatially dependent changes in action potential duration (APD) in homogeneous and isotropic tissue, where all the cells have the same APD in the absence of diffusion. Electrotonic currents due to coupling within the tissue and at the tissue boundaries can generate dispersion, and the profile of this dispersion can change dramatically depending on tissue size and shape, action potential morphology, tissue dimensionality, and stimulus frequency and location. The dispersion generated by pure geometrical effects can be on the order of tens of milliseconds, enough under certain conditions to produce conduction blocks and initiate reentrant waves. PMID:21762703

Anti-addiction Drug Ibogaine Prolongs the Action Potential in Human Induced Pluripotent Stem Cell-Derived Cardiomyocytes.

PubMed

Rubi, Lena; Eckert, Daniel; Boehm, Stefan; Hilber, Karlheinz; Koenig, Xaver

2017-04-01

Ibogaine is a plant alkaloid used as anti-addiction drug in dozens of alternative medicine clinics worldwide. Recently, alarming reports of life-threatening cardiac arrhythmias and cases of sudden death associated with the ingestion of ibogaine have accumulated. Using whole-cell patch clamp recordings, we assessed the effects of ibogaine and its main metabolite noribogaine on action potentials in human ventricular-like cardiomyocytes derived from induced pluripotent stem cells. Therapeutic concentrations of ibogaine and its long-lived active metabolite noribogaine significantly retarded action potential repolarization in human cardiomyocytes. These findings represent the first experimental proof that ibogaine application entails a cardiac arrhythmia risk for humans. In addition, they explain the clinically observed delayed incidence of cardiac adverse events several days after ibogaine intake. We conclude that therapeutic concentrations of ibogaine retard action potential repolarization in the human heart. This may give rise to a prolongation of the QT interval in the electrocardiogram and cardiac arrhythmias.

An indirect component in the evoked compound action potential of the vagal nerve.

PubMed

Ordelman, Simone C M A; Kornet, Lilian; Cornelussen, Richard; Buschman, Hendrik P J; Veltink, Peter H

2010-12-01

The vagal nerve plays a vital role in the regulation of the cardiovascular system. It not only regulates the heart but also sends sensory information from the heart back to the brain. We hypothesize that the evoked vagal nerve compound action potential contains components that are indirect via the brain stem or coming via the neural network on the heart. In an experimental study of 15 pigs, we identified four components in the evoked compound action potentials. The fourth component was found to be an indirect component, which came from the periphery. The latency of the indirect component increased when heart rate and contractility were decreased by burst stimulation (P = 0.01; n = 7). When heart rate and contractility were increased by dobutamine administration, the latency of the indirect component decreased (P = 0.01; n = 9). This showed that the latency of the indirect component of the evoked compound action potentials may relate to the state of the cardiovascular system.

[Effects of 2-(p-dimethylaminostyryl) pyridine methycholide (DSPM-Ci) on ECG, left atrium contractivity and on papillary muscle action potentials].

PubMed

Jiang, X Y; Zhou, C M; Li, D M; Zhang, K J

1996-01-01

The effects of DSPM-Cl on ECG in rats, on the dose-effect curve in guinea pig left atria and on the fast action potential (AP), high-K+ depolarized slow action potential (SAP) in guinea pigs papillary muscle were examined electrophysiologically. DSPM-Cl (2 mg.kg-1) showed significant nagative frequency, negative conductivity effect, and prolonged the PP and PR interval. DSPM-CI (30-50 mumol.L-1) was shown to inhibit left atria contractility and shift the concentration-response curve of Iso and CaCl2 to the right with PD2' values of 4.60 and 4.13, respectively. In addition, DSPM-Cl was found to prolong the duration of action potential 90 (APD90) and effective refractory period (ERP), and decrease the maximal upstroke velocity (Vmax) in K(+)-depolarized guinea pigs papillary muscles. The results suggest that, like verpamil, DSPM-Cl might be a calcium antagonist.

Action potential-independent and pharmacologically unique vesicular serotonin release from dendrites

PubMed Central

Colgan, Lesley A.; Cavolo, Samantha L.; Commons, Kathryn G.; Levitan, Edwin S.

2012-01-01

Serotonin released within the dorsal raphe nucleus (DR) induces feedback inhibition of serotonin neuron activity and consequently regulates mood-controlling serotonin release throughout the forebrain. Serotonin packaged in vesicles is released in response to action potentials by the serotonin neuron soma and terminals, but the potential for release by dendrites is unknown. Here three-photon (3P) microscopy imaging of endogenous serotonin in living rat brain slice, immunofluorescence and immuno-gold electron microscopy detection of VMAT2 (vesicular monoamine transporter 2) establish the presence of vesicular serotonin within DR dendrites. Furthermore, activation of glutamate receptors is shown to induce vesicular serotonin release from dendrites. However, unlike release from the soma and terminals, dendritic serotonin release is independent of action potentials, relies on L-type Ca2+ channels, is induced preferentially by NMDA, and displays distinct sensitivity to the selective serotonin reuptake inhibitor (SSRI) antidepressant fluoxetine. The unique control of dendritic serotonin release has important implications for DR physiology and the antidepressant action of SSRIs, dihydropyridines and NMDA receptor antagonists. PMID:23136413

(2R,3S,2”R,3”R)-manniflavanone, a new gastrointestinal smooth muscle L-type calcium channel inhibitor, which underlies the spasmolytic properties of Garcinia buchananii stem bark extract

PubMed Central

Balemba, Onesmo B.; Stark, Timo D.; Lösch, Sofie; Patterson, Savannah; McMillan, John S.; Mawe, Gary M.; Hofmann, Thomas

2014-01-01

Garcinia buchananii Baker stem bark extract (GBB) is a traditional medication of diarrhea and dysentery in sub-Saharan Africa. It is believed that GBB causes gastrointestinal smooth muscle relaxation. The aim of this study was to determine whether GBB has spasmolytic actions and identify compounds underlying these actions. Calcium (Ca2+) imaging was used to analyze the effect of GBB on Ca2+ flashes and Ca2+ waves in guinea pig gallbladder and distal colon smooth muscle. Intracellular microelectrode recording was used to determine the effect of GBB, six fractions of GBB, M1–5 and M7, and (2R,3S,2”R,3”R)-manniflavanone, a compound isolated from M3 on action potentials in gallbladder smooth muscle. The technique was also used to analyze the effect of GBB, M3, and (2R,3S,2”R,3”R)-manniflavanone on action potentials in the circular muscle of mouse and guinea pig distal colons, and the effect of GBB and (2R,3S,2”R,3”R)-manniflavanone on slow waves in porcine ileum. GBB inhibited Ca2+ flashes and Ca2+ waves. GBB, M3 and (2R,3S,2”R,3”R)-manniflavanone inhibited action potentials. L-type Ca2+ channel activator Bay K 8644 increased the discharge of action potentials in mouse colon but did not trigger or increase action potentials in the presence of GBB and (2R,3S,2”R,3”R)-manniflavanone. GBB and (2R,3S,2”R,3”R)-manniflavanone inhibited action potentials in the presence of Bay K 8644. GBB and (2R,3S,2”R,3”R)-manniflavanone reduced the amplitude but did not alter the frequency of slow waves in the porcine ileum. In conclusion, GBB and (2R,3S,2”R,3”R)-manniflavanone relax smooth muscle by inhibiting L-type Ca2+ channels, thus have potential for use as therapies of gastrointestinal smooth muscle spasms, and arrhythmias. PMID:26081368

Reactive species modify NaV1.8 channels and affect action potentials in murine dorsal root ganglia neurons

PubMed Central

Schink, Martin; Leipolcf, Enrico; Schirmeyer, Jana; Schönherr, Roland; Hoshi, Toshinori; Heinemann, Stefan H.

2016-01-01

Dorsal root ganglia (DRG) neurons are important relay stations between the periphery and the central nervous system and are essential for somatosensory signaling. Reactive species are produced in a variety of physiological and pathophysiological conditions and are known to alter electric signaling. Here we studied the influence of reactive species on the electrical properties of DRG neurons from mice with the whole-cell patch-clamp method. Even mild stress induced by either low concentrations of chloramine-T (10 µM) or low-intensity blue-light irradiation profoundly diminished action potential frequency but prolonged single action potentials in wild-type neurons. The impact on evoked action potentials was much smaller in neurons deficient of the tetrodotoxin (TTX)-resistant voltage-gated sodium channel NaV1.8 (NaV1.8−/−), the channel most important for the action potential upstroke in DRG neurons. Low concentrations of chloramine-T caused a significant reduction of NaV1.8 peak current and at higher concentrations progressively slowed down inactivation. Blue light had a smaller effect on amplitude but slowed down NaV1.8 channel inactivation. The observed effects were less apparent for TTX-sensitive NaV channels. NaV1.8 is an important reactive-species-sensitive component in the electrical signaling of DRG neurons, potentially giving rise to loss-of-function and gain-of-function phenomena depending on the type of reactive species and their effective concentration and time of exposure. PMID:26383867

Ranolazine inhibits shear sensitivity of endogenous Na+ current and spontaneous action potentials in HL-1 cells

PubMed Central

Strege, Peter; Beyder, Arthur; Bernard, Cheryl; Crespo-Diaz, Ruben; Behfar, Atta; Terzic, Andre; Ackerman, Michael; Farrugia, Gianrico

2012-01-01

NaV1.5 is a mechanosensitive voltage-gated Na+ channel encoded by the gene SCN5A, expressed in cardiac myocytes and required for phase 0 of the cardiac action potential (AP). In the cardiomyocyte, ranolazine inhibits depolarizing Na+ current and delayed rectifier (IKr) currents. Recently, ranolazine was also shown to be an inhibitor of NaV1.5 mechanosensitivity. Stretch also accelerates the firing frequency of the SA node, and fluid shear stress increases the beating rate of cultured cardiomyocytes in vitro. However, no cultured cell platform exists currently for examination of spontaneous electrical activity in response to mechanical stimulation. In the present study, flow of solution over atrial myocyte-derived HL-1 cultured cells was used to study shear stress mechanosensitivity of Na+ current and spontaneous, endogenous rhythmic action potentials. In voltage-clamped HL-1 cells, bath flow increased peak Na+ current by 14 ± 5%. In current-clamped cells, bath flow increased the frequency and decay rate of AP by 27 ± 12% and 18 ± 4%, respectively. Ranolazine blocked both responses to shear stress. This study suggests that cultured HL-1 cells are a viable in vitro model for detailed study of the effects of mechanical stimulation on spontaneous cardiac action potentials. Inhibition of the frequency and decay rate of action potentials in HL-1 cells are potential mechanisms behind the antiarrhythmic effect of ranolazine. PMID:23018927

Reactive species modify NaV1.8 channels and affect action potentials in murine dorsal root ganglion neurons.

PubMed

Schink, Martin; Leipold, Enrico; Schirmeyer, Jana; Schönherr, Roland; Hoshi, Toshinori; Heinemann, Stefan H

2016-01-01

Dorsal root ganglion (DRG) neurons are important relay stations between the periphery and the central nervous system and are essential for somatosensory signaling. Reactive species are produced in a variety of physiological and pathophysiological conditions and are known to alter electric signaling. Here we studied the influence of reactive species on the electrical properties of DRG neurons from mice with the whole-cell patch-clamp method. Even mild stress induced by either low concentrations of chloramine-T (10 μM) or low-intensity blue light irradiation profoundly diminished action potential frequency but prolonged single action potentials in wild-type neurons. The impact on evoked action potentials was much smaller in neurons deficient of the tetrodotoxin (TTX)-resistant voltage-gated sodium channel NaV1.8 (NaV1.8(-/-)), the channel most important for the action potential upstroke in DRG neurons. Low concentrations of chloramine-T caused a significant reduction of NaV1.8 peak current and, at higher concentrations, progressively slowed down inactivation. Blue light had a smaller effect on amplitude but slowed down NaV1.8 channel inactivation. The observed effects were less apparent for TTX-sensitive NaV channels. NaV1.8 is an important reactive-species-sensitive component in the electrical signaling of DRG neurons, potentially giving rise to loss-of-function and gain-of-function phenomena depending on the type of reactive species and their effective concentration and time of exposure.

TRH regulates action potential shape in cerebral cortex pyramidal neurons.

PubMed

Rodríguez-Molina, Víctor; Patiño, Javier; Vargas, Yamili; Sánchez-Jaramillo, Edith; Joseph-Bravo, Patricia; Charli, Jean-Louis

2014-07-07

Thyrotropin releasing hormone (TRH) is a neuropeptide with a wide neural distribution and a variety of functions. It modulates neuronal electrophysiological properties, including resting membrane potential, as well as excitatory postsynaptic potential and spike frequencies. We explored, with whole-cell patch clamp, TRH effect on action potential shape in pyramidal neurons of the sensorimotor cortex. TRH reduced spike and after hyperpolarization amplitudes, and increased spike half-width. The effect varied with dose, time and cortical layer. In layer V, 0.5µM of TRH induced a small increase in spike half-width, while 1 and 5µM induced a strong but transient change in spike half-width, and amplitude; after hyperpolarization amplitude was modified at 5µM of TRH. Cortical layers III and VI neurons responded intensely to 0.5µM TRH; layer II neurons response was small. The effect of 1µM TRH on action potential shape in layer V neurons was blocked by G-protein inhibition. Inhibition of the activity of the TRH-degrading enzyme pyroglutamyl peptidase II (PPII) reproduced the effect of TRH, with enhanced spike half-width. Many cortical PPII mRNA+ cells were VGLUT1 mRNA+, and some GAD mRNA+. These data show that TRH regulates action potential shape in pyramidal cortical neurons, and are consistent with the hypothesis that PPII controls its action in this region. Copyright © 2014 Elsevier B.V. All rights reserved.

Diuretic‐sensitive electroneutral Na+ movement and temperature effects on central axons

PubMed Central

Kanagaratnam, Meneka; Pendleton, Christopher; Souza, Danilo Almeida; Pettit, Joseph; Howells, James

2017-01-01

Key points Optic nerve axons get less excitable with warming.F‐fibre latency does not shorten at temperatures above 30°C.Action potential amplitude falls when the Na+‐pump is blocked, an effect speeded by warming.Diuretics reduce the rate of action potential fall in the presence of ouabain.Our data are consistent with electroneutral entry of Na+ occurring in axons and contributing to setting the resting potential. Abstract Raising the temperature of optic nerve from room temperature to near physiological has effects on the threshold, refractoriness and superexcitability of the shortest latency (fast, F) nerve fibres, consistent with hyperpolarization. The temperature dependence of peak impulse latency was weakened at temperatures above 30°C suggesting a temperature‐sensitive process that slows impulse propagation. The amplitude of the supramaximal compound action potential gets larger on warming, whereas in the presence of bumetanide and amiloride (blockers of electroneutral Na+ movement), the action potential amplitude consistently falls. This suggests a warming‐induced hyperpolarization that is reduced by blocking electroneutral Na+ movement. In the presence of ouabain, the action potential collapses. This collapse is speeded by warming, and exposure to bumetanide and amiloride slows the temperature‐dependent amplitude decline, consistent with a warming‐induced increase in electroneutral Na+ entry. Blocking electroneutral Na+ movement is predicted to be useful in the treatment of temperature‐dependent symptoms under conditions with reduced safety factor (Uhthoff's phenomenon) and provide a route to neuroprotection. PMID:28213919

Control of CA3 output by feedforward inhibition despite developmental changes in the excitation-inhibition balance.

PubMed

Torborg, Christine L; Nakashiba, Toshiaki; Tonegawa, Susumu; McBain, Chris J

2010-11-17

In somatosensory cortex, the relative balance of excitation and inhibition determines how effectively feedforward inhibition enforces the temporal fidelity of action potentials. Within the CA3 region of the hippocampus, glutamatergic mossy fiber (MF) synapses onto CA3 pyramidal cells (PCs) provide strong monosynaptic excitation that exhibit prominent facilitation during repetitive activity. We demonstrate in the juvenile CA3 that MF-driven polysynaptic IPSCs facilitate to maintain a fixed EPSC-IPSC ratio during short-term plasticity. In contrast, in young adult mice this MF-driven polysynaptic inhibitory input can facilitate or depress in response to short trains of activity. Transgenic mice lacking the feedback inhibitory loop continue to exhibit both facilitating and depressing polysynaptic IPSCs, indicating that this robust inhibition is not caused by the secondary engagement of feedback inhibition. Surprisingly, eliminating MF-driven inhibition onto CA3 pyramidal cells by blockade of GABA(A) receptors did not lead to a loss of temporal precision of the first action potential observed after a stimulus but triggered in many cases a long excitatory plateau potential capable of triggering repetitive action potential firing. These observations indicate that, unlike other regions of the brain, the temporal precision of single MF-driven action potentials is dictated primarily by the kinetics of MF EPSPs, not feedforward inhibition. Instead, feedforward inhibition provides a robust regulation of CA3 PC excitability across development to prevent excessive depolarization by the monosynaptic EPSP and multiple action potential firings.

Human stem cell-derived cardiomyocytes detect drug-mediated changes in action potentials and ion currents.

PubMed

Gibson, John K; Yue, Yimei; Bronson, Jared; Palmer, Cassie; Numann, Randy

2014-01-01

It has been proposed that proarrhythmia assessment for safety pharmacology testing includes the use of human pluripotent stem cell-derived cardiomyocytes (hiPSC-CM) to detect drug-induced changes in cardiac electrophysiology. This study measured the actions of diverse agents on action potentials (AP) and ion currents recorded from hiPSC-CM. During AP experiments, the hiPSC-CM were paced at 1Hz during a baseline period, and when increasing concentrations of test compound were administered at 4-minute intervals. AP parameters, including duration (APD60 and APD90), resting membrane potential, rate of rise, and amplitude, were measured throughout the entire experiment. Voltage clamp experiments with E-4031 and nifedipine were similarly conducted. E-4031 produced a dose-dependent prolongation of cardiac action potential and blocked the hERG/IKr current with an IC50 of 17nM. At 3nM, dofetilide significantly increased APD90. Astemizole significantly increased APD60 and APD90 at 30nM. Terfenadine significantly increased APD90 at concentrations greater than 10nM. Fexofenadine, a metabolite of terfenadine, did not produce any electrophysiologic changes in cardiac action potentials. Flecainide produced a dose-dependent prolongation of the cardiac action potential at 1 and 3μM. Acute exposure to nifedipine significantly decreased APD60 and APD90 and produced a dose-dependent block of calcium current with an IC50 of 0.039μM. Verapamil first shortened APD60 and APD90 in a dose-dependent manner, until a compensating increase in APD90, presumably via hERG blockade, was observed at 1 and 3μM. Following a chronic exposure (20-24h) to clinically relevant levels of pentamidine, a significant increase in action potential duration was accompanied by early afterdepolarizations (EADs). These experiments show the ability of AP measured from hiPSC-CM to record the interactions of various ion channels via AP recording and avoid the limitations of using several single ion channel assays in a noncardiac tissue. Copyright © 2014 Elsevier Inc. All rights reserved.

Membrane, action, and oscillatory potentials in simulated protocells

NASA Technical Reports Server (NTRS)

Syren, R. M.; Fox, S. W.; Przybylski, A. T.; Stratten, W. P.

1982-01-01

Electrical membrane potentials, oscillations, and action potentials are observed in proteinoid microspheres impaled with (3 M KCl) microelectrodes. Although effects are of greater magnitude when the vesicles contain glycerol and natural or synthetic lecithin, the results in the purely synthetic thermal protein structures are substantial, attaining 20 mV amplitude in some cases. The results add the property of electrical potential to the other known properties of proteinoid microspheres, in their role as models for protocells.

[The influence of various acoustic stimuli upon the cumulative action potential (SAP) of the auditory nerves in guinea pigs (author's transl)].

PubMed

Hofmann, G; Kraak, W

1976-08-31

The impact of various acoustic stimuli upon the cumulative action potential of the auditory nerves in guinea pigs is investigated by means of the averaging method. It was found that the potential amplitude within the measuring range increases with the logarithm of the rising sonic pressure velocity. Unlike the evoked response audiometry (ERA), this potential seems unsuitable for furnishing information of the frequency-dependent threshold course.

77 FR 75390 - Significant New Use Rules on Certain Chemical Substances

Federal Register 2010, 2011, 2012, 2013, 2014

2012-12-20

... Agency (EPA). ACTION: Direct final rule. SUMMARY: EPA is promulgating significant new use rules (SNURs... subject of premanufacture notices (PMNs). This action requires persons who intend to manufacture, import... this action apply to me? You may be potentially affected by this action if you manufacture, import...

Optical recording of action potentials and other discrete physiological events: a perspective from signal detection theory.

PubMed

Sjulson, Lucas; Miesenböck, Gero

2007-02-01

Optical imaging of physiological events in real time can yield insights into biological function that would be difficult to obtain by other experimental means. However, the detection of all-or-none events, such as action potentials or vesicle fusion events, in noisy single-trial data often requires a careful balance of tradeoffs. The analysis of such experiments, as well as the design of optical reporters and instrumentation for them, is aided by an understanding of the principles of signal detection. This review illustrates these principles, using as an example action potential recording with optical voltage reporters.

Pb2+ Modulates Ca2+ Membrane Permeability In Paramecium

NASA Astrophysics Data System (ADS)

Bernal-Martínez, Juan; Ortega Soto, Arturo

2004-09-01

Intracellular recording experiments in current clamp configuration were done to evaluate whether Pb2+ modulates ionic membrane permeability in the fresh water Paramecium tetraurelia. It was found that Pb2+ triggers in a dose-dependent manner, a burst of spontaneous action potentials followed by a robust and sustained after hyper-polarization. In addition, Pb2+ increased the frequency of firing the spontaneous Ca2+-Action Potential and also, the duration of Ca2+-Action Potential, in a dose and reversibly-dependent manner. These results suggest that Pb2+ increases calcium membrane permeability of Paramecium and probably activates a calcium-dependent-potassium conductance in the ciliate.

Monophasic action potentials of right atrium and electrophysiological properties of AV conducting system in patients with hypothyroidism.

PubMed Central

Gavrilescu, S; Luca, C; Streian, C; Lungu, G; Deutsch, G

1976-01-01

In 12 patients with manifest hypothyroidism right atrial monophasic action potentials showed a significant prolongation in comparison with data from normal or euthyroid patients. Atrial effective refractory periods were also significantly prolonged. After thyroid treatment the monophasic action potential duration and the effective refractory period of the right atrium were within normal ranges. In 6 hypothyroid patients studies of AV conduction with the aid of His bundle electrography and atrial pacing showed a supraHisian conduction delay which was manifest in one case and latent in another two. InfraHisian conduction delay was encountered in 2 cases. PMID:1008978

Action of bradykinin potentiating factor (BPF) and dimercaprol (BAL) on the responses to bradykinin of isolated preparations of rat intestines.

PubMed

Camargo, A; Ferreira, S H

1971-06-01

BPF and BAL inhibited kininase activity of homogenates of rat intestine. However, BFP potentiated and BAL inhibited the contractions induced by bradykinin on rat isolated duodenum (low calcium solution) and terminal ileum (normal calcium solution). Neither BPF nor BAL affects the relaxation induced by bradykinin of rat duodenum bathed in normal Tyrode. These results suggest that two different types of pharmacological receptor are involved in the action of bradykinin on rat intestine, and that other factors besides the inhibition of agonist destruction participate in the mechanism of potentiation of kinin action by BPF.

Action of bradykinin potentiating factor (BPF) and dimercaprol (BAL) on the responses to bradykinin of isolated preparations of rat intestines

PubMed Central

Camargo, A.; Ferreira, S. H.

1971-01-01

BPF and BAL inhibited kininase activity of homogenates of rat intestine. However, BFP potentiated and BAL inhibited the contractions induced by bradykinin on rat isolated duodenum (low calcium solution) and terminal ileum (normal calcium solution). Neither BPF nor BAL affects the relaxation induced by bradykinin of rat duodenum bathed in normal Tyrode. These results suggest that two different types of pharmacological receptor are involved in the action of bradykinin on rat intestine, and that other factors besides the inhibition of agonist destruction participate in the mechanism of potentiation of kinin action by BPF. PMID:5091164

External Cooling of the BWR Mark I and II Drywell Head as a Potential Accident Mitigation Measure – Scoping Assessment

DOE Office of Scientific and Technical Information (OSTI.GOV)

Robb, Kevin R.

This report documents a scoping assessment of a potential accident mitigation action applicable to the US fleet of boiling water reactors with Mark I and II containments. The mitigation action is to externally flood the primary containment vessel drywell head using portable pumps or other means. A scoping assessment of the potential benefits of this mitigation action was conducted focusing on the ability to (1) passively remove heat from containment, (2) prevent or delay leakage through the drywell head seal (due to high temperatures and/or pressure), and (3) scrub radionuclide releases if the drywell head seal leaks.

Defense Science Board (DSB) Summer Study Report on Strategic Surprise

DTIC Science & Technology

2015-07-01

against changing priorities. The study focused on potential regrets in eight areas and provides recommendations to avoid strategic surprise in those...explore potential changes for  Department of Defense priorities as well as possible actions and hedges to strategic surprise and  avoid   potential  regrets ...similar surprises—and to  avoid   regretting  actions or lack  of action taken today—the study evaluated several key mission and enterprise areas. Some of

Reliability of directional information in unsorted spikes and local field potentials recorded in human motor cortex

PubMed Central

Perge, János A.; Zhang, Shaomin; Malik, Wasim Q.; Homer, Mark L.; Cash, Sydney; Friehs, Gerhard; Eskandar, Emad N.; Donoghue, John P.; Hochberg, Leigh R.

2014-01-01

Objective Action potentials and local field potentials (LFPs) recorded in primary motor cortex contain information about the direction of movement. LFPs are assumed to be more robust to signal instabilities than action potentials, which makes LFPs along with action potentials a promising signal source for brain-computer interface applications. Still, relatively little research has directly compared the utility of LFPs to action potentials in decoding movement direction in human motor cortex. Approach We conducted intracortical multielectrode recordings in motor cortex of two persons (T2 and [S3]) as they performed a motor imagery task. We then compared the offline decoding performance of LFPs and spiking extracted from the same data recorded across a one-year period in each participant. Main results We obtained offline prediction accuracy of movement direction and endpoint velocity in multiple LFP bands, with the best performance in the highest (200–400Hz) LFP frequency band, presumably also containing low-pass filtered action potentials. Cross-frequency correlations of preferred directions and directional modulation index showed high similarity of directional information between action potential firing rates (spiking) and high frequency LFPs (70–400Hz), and increasing disparity with lower frequency bands (0–7, 10–40 and 50–65Hz). Spikes predicted the direction of intended movement more accurately than any individual LFP band, however combined decoding of all LFPs was statistically indistinguishable from spike based performance. As the quality of spiking signals (i.e. signal amplitude) and the number of significantly modulated spiking units decreased, the offline decoding performance decreased 3.6[5.65]%/month (for T2 and [S3] respectively). The decrease in the number of significantly modulated LFP signals and their decoding accuracy followed a similar trend (2.4[2.85]%/month, ANCOVA, p=0.27[0.03]). Significance Field potentials provided comparable offline decoding performance to unsorted spikes. Thus, LFPs may provide useful external device control using current human intracortical recording technology. (Clinical trial registration number: NCT00912041) PMID:24921388

Increased transient Na+ conductance and action potential output in layer 2/3 prefrontal cortex neurons of the fmr1-/y mouse.

PubMed

Routh, Brandy N; Rathour, Rahul K; Baumgardner, Michael E; Kalmbach, Brian E; Johnston, Daniel; Brager, Darrin H

2017-07-01

Layer 2/3 neurons of the prefrontal cortex display higher gain of somatic excitability, responding with a higher number of action potentials for a given stimulus, in fmr1 -/y mice. In fmr1 -/y L2/3 neurons, action potentials are taller, faster and narrower. Outside-out patch clamp recordings revealed that the maximum Na + conductance density is higher in fmr1 -/y L2/3 neurons. Measurements of three biophysically distinct K + currents revealed a depolarizing shift in the activation of a rapidly inactivating (A-type) K + conductance. Realistic neuronal simulations of the biophysical observations recapitulated the elevated action potential and repetitive firing phenotype. Fragile X syndrome is the most common form of inherited mental impairment and autism. The prefrontal cortex is responsible for higher order cognitive processing, and prefrontal dysfunction is believed to underlie many of the cognitive and behavioural phenotypes associated with fragile X syndrome. We recently demonstrated that somatic and dendritic excitability of layer (L) 5 pyramidal neurons in the prefrontal cortex of the fmr1 -/y mouse is significantly altered due to changes in several voltage-gated ion channels. In addition to L5 pyramidal neurons, L2/3 pyramidal neurons play an important role in prefrontal circuitry, integrating inputs from both lower brain regions and the contralateral cortex. Using whole-cell current clamp recording, we found that L2/3 pyramidal neurons in prefrontal cortex of fmr1 -/y mouse fired more action potentials for a given stimulus compared with wild-type neurons. In addition, action potentials in fmr1 -/y neurons were significantly larger, faster and narrower. Voltage clamp of outside-out patches from L2/3 neurons revealed that the transient Na + current was significantly larger in fmr1 -/y neurons. Furthermore, the activation curve of somatic A-type K + current was depolarized. Realistic conductance-based simulations revealed that these biophysical changes in Na + and K + channel function could reliably reproduce the observed increase in action potential firing and altered action potential waveform. These results, in conjunction with our prior findings on L5 neurons, suggest that principal neurons in the circuitry of the medial prefrontal cortex are altered in distinct ways in the fmr1 -/y mouse and may contribute to dysfunctional prefrontal cortex processing in fragile X syndrome. © 2017 The Authors. The Journal of Physiology © 2017 The Physiological Society.

'Long-Cell Action' Corrosion: A Basic Mechanism Hidden Behind Components Degradation Issues in Nuclear Power Plants

DOE Office of Scientific and Technical Information (OSTI.GOV)

Genn Saji

2006-07-01

In spite of industries' effort over the last 40 years, corrosion-related issues continue to be one of the largest unresolved problems for nuclear power plants worldwide. There are several types of strange corrosion phenomena from the point of view of our current understanding of corrosion science established in other fields. Some of these are IGSCC, PWSCC, AOA, and FAC (Erosion-Corrosion). Through studying and coping with diverse corrosion phenomena, the author believes that they share a common basis with respect to the assumed corrosion mechanism (e.g., 'local cell action' hypothesis). In general, local cell action is rarely severe since it producesmore » a fairly uniform corrosion. The 'long cell action' that transports electrons through structures far beyond the region of local cell corrosion activities has been identified as a basic mechanism in soil corrosion. If this mechanism is assumed in nuclear power plants, the structure becomes anodic in the area where the potential is less positive and cathodic where this potential is more positive. Metallic ions generated at anodic corrosion sites are transported to remote cathodic sites through the circulation of water and deposits as corrosion products. The SCC, FAC (E-C) and PWSCC occur in the anodic sites as the structure itself acts as a short-circuiting conductor between the two sites, the action is similar to a galvanic cell but in a very large scale. This situation is the same as a battery that has been short-circuited at the terminals. No apparent external potential difference exists between the two electrodes, but an electrochemical reaction is still taking place inside the battery cell with a large internal short current. In this example what is important is the potential difference between the local coolant and the surface of the structural material. Long cell action corrosion is likely enhancing the local cell action's anodic corrosion activities, such as SCC, FAC/E-C, and PWSCC. It tends to be more hazardous because of its localized nature compared with the local cell action corrosion. There exist various mechanisms (electrochemical cell configurations) that induce such potential differences, including: ionic concentration, aeration, temperature, flow velocity, radiation and corrosion potentials. In this paper, the author will discuss these potential differences and their relevance to the un-resolved corrosion issues in nuclear power plants. Due to the importance of this potential mechanism the author is calling for further verification experiments as a joint international project. (author)« less

Differential roles of two delayed rectifier potassium currents in regulation of ventricular action potential duration and arrhythmia susceptibility.

PubMed

Devenyi, Ryan A; Ortega, Francis A; Groenendaal, Willemijn; Krogh-Madsen, Trine; Christini, David J; Sobie, Eric A

2017-04-01

Arrhythmias result from disruptions to cardiac electrical activity, although the factors that control cellular action potentials are incompletely understood. We combined mathematical modelling with experiments in heart cells from guinea pigs to determine how cellular electrical activity is regulated. A mismatch between modelling predictions and the experimental results allowed us to construct an improved, more predictive mathematical model. The balance between two particular potassium currents dictates how heart cells respond to perturbations and their susceptibility to arrhythmias. Imbalances of ionic currents can destabilize the cardiac action potential and potentially trigger lethal cardiac arrhythmias. In the present study, we combined mathematical modelling with information-rich dynamic clamp experiments to determine the regulation of action potential morphology in guinea pig ventricular myocytes. Parameter sensitivity analysis was used to predict how changes in ionic currents alter action potential duration, and these were tested experimentally using dynamic clamp, a technique that allows for multiple perturbations to be tested in each cell. Surprisingly, we found that a leading mathematical model, developed with traditional approaches, systematically underestimated experimental responses to dynamic clamp perturbations. We then re-parameterized the model using a genetic algorithm, which allowed us to estimate ionic current levels in each of the cells studied. This unbiased model adjustment consistently predicted an increase in the rapid delayed rectifier K + current and a drastic decrease in the slow delayed rectifier K + current, and this prediction was validated experimentally. Subsequent simulations with the adjusted model generated the clinically relevant prediction that the slow delayed rectifier is better able to stabilize the action potential and suppress pro-arrhythmic events than the rapid delayed rectifier. In summary, iterative coupling of simulations and experiments enabled novel insight into how the balance between cardiac K + currents influences ventricular arrhythmia susceptibility. © 2016 The Authors. The Journal of Physiology © 2016 The Physiological Society.

Analysis of electrically evoked compound action potential of the auditory nerve in children with bilateral cochlear implants.

PubMed

Caldas, Fernanda Ferreira; Cardoso, Carolina Costa; Barreto, Monique Antunes de Souza Chelminski; Teixeira, Marina Santos; Hilgenberg, Anacléia Melo da Silva; Serra, Lucieny Silva Martins; Bahmad Junior, Fayez

2016-01-01

The cochlear implant device has the capacity to measure the electrically evoked compound action potential of the auditory nerve. The neural response telemetry is used in order to measure the electrically evoked compound action potential of the auditory nerve. To analyze the electrically evoked compound action potential, through the neural response telemetry, in children with bilateral cochlear implants. This is an analytical, prospective, longitudinal, historical cohort study. Six children, aged 1-4 years, with bilateral cochlear implant were assessed at five different intervals during their first year of cochlear implant use. There were significant differences in follow-up time (p=0.0082) and electrode position (p=0.0019) in the T-NRT measure. There was a significant difference in the interaction between time of follow-up and electrode position (p=0.0143) when measuring the N1-P1 wave amplitude between the three electrodes at each time of follow-up. The electrically evoked compound action potential measurement using neural response telemetry in children with bilateral cochlear implants during the first year of follow-up was effective in demonstrating the synchronized bilateral development of the peripheral auditory pathways in the studied population. Copyright © 2015 Associação Brasileira de Otorrinolaringologia e Cirurgia Cérvico-Facial. Published by Elsevier Editora Ltda. All rights reserved.

Temporary hearing loss influences post-stimulus time histogram and single neuron action potential estimates from human compound action potentials

PubMed Central

Lichtenhan, Jeffery T.; Chertoff, Mark E.

2008-01-01

An analytic compound action potential (CAP) obtained by convolving functional representations of the post-stimulus time histogram summed across auditory nerve neurons [P(t)] and a single neuron action potential [U(t)] was fit to human CAPs. The analytic CAP fit to pre- and postnoise-induced temporary hearing threshold shift (TTS) estimated in vivoP(t) and U(t) and the number of neurons contributing to the CAPs (N). The width of P(t) decreased with increasing signal level and was wider at the lowest signal level following noise exposure. P(t) latency decreased with increasing signal level and was shorter at all signal levels following noise exposure. The damping and oscillatory frequency of U(t) increased with signal level. For subjects with large amounts of TTS, U(t) had greater damping than before noise exposure particularly at low signal levels. Additionally, U(t) oscillation was lower in frequency at all click intensities following noise exposure. N increased with signal level and was smaller after noise exposure at the lowest signal level. Collectively these findings indicate that neurons contributing to the CAP during TTS are fewer in number, shorter in latency, and poorer in synchrony than before noise exposure. Moreover, estimates of single neuron action potentials may decay more rapidly and have a lower oscillatory frequency during TTS. PMID:18397026

CORRECTIVE ACTION DECISION DOCUMENT FOR AREA 9 UXO LANDFILL, TONOPAH TEST RNGE, CAU 453, REVISION 0, MARCH 1998

DOE Office of Scientific and Technical Information (OSTI.GOV)

none

1998-03-01

This Corrective Action Decision Document (CADD) has been prepared for the Area 9 Unexploded Ordnance (UXO) Landfill (Corrective Action Unit [CAU] 453) in accordance with the Federal Facility Agreement and Consent Order (FFACO) of 1996. Corrective Action Unit 453 is located at the Tonopah Test Range (TTR), Nevada, and is comprised of three individual landfill cells located northwest of Area 9. The cells are listed as one Corrective Action Site (CAS) 09-55-001-0952. The landfill cells have been designated as: � Cell A9-1 � Cell A9-2 � Cell A9-3 The purpose of this CADD is to identify and provide a rationalemore » for the selection of a recommended corrective action alternative for CAU 453. The scope of this CADD consists of the following tasks: � Develop corrective action objectives. � Identify corrective action alternative screening criteria. � Develop corrective action alternatives. � Perform detailed and comparative evaluations of the corrective action alternatives in relation to the corrective action objectives and screening criteria. � Recommend and justify a preferred corrective action alternative for the CAU. In June and July 1997, a corrective action investigation was performed that consisted of activities set forth in the Corrective Action Investigation Plan (CAIP) (DOE/NV, 1997). Subsurface investigation of the soils surrounding the cells revealed no contaminants of concern (COCs) above preliminary action levels. The cell contents were not investigated due to the potential for live UXO. Details concerning the analytical and investigation results can be found in Appendix A of this CADD. Based on the potential exposure pathways, the following corrective action objectives have been identified for CAU 453: � Prevent or mitigate human exposure to subsurface soils containing COCs, solid waste, and/or UXO. � Prevent adverse impacts to groundwater quality. Based on the review of existing data, future land use, and current operations at the TTR, the following alternatives have been developed for consideration at the Area 9 UXO Landfill CAU: � Alternative 1 - No Further Action � Alternative 2 - Closure in Place by Administrative Controls � Alternative 3 - Closure in Place by Capping � Alternative 4 - Clean Closure by Removal The corrective action alternatives were evaluated based on four general corrective action standards and five remedy selection decision factors. Based on the results of this evaluation, Alternative 2, Closure in Place by Administrative Controls, was selected as the preferred corrective action alternative. The preferred corrective action alternative was evaluated on its technical merits, focusing on performance, reliability, feasibility, and safety. The alternative was judged to meet all requirements for the technical components evaluated and to represent the most cost-effective corrective action. The alternative meets all applicable state and federal regulations for closure of the site and will reduce potential future exposure pathways to the contents of the landfill. During corrective action implementation, this alternative will present minimal potential threat to site workers. However, appropriate health and safety procedures will be developed and implemented.« less

SL(2,R) duality-symmetric action for electromagnetic theory with electric and magnetic sources

DOE Office of Scientific and Technical Information (OSTI.GOV)

Lee, Choonkyu, E-mail: cklee@phya.snu.ac.kr; School of Physics, Korea Institute for Advanced Study, Seoul 130-722; Min, Hyunsoo, E-mail: hsmin@dirac.uos.ac.kr

2013-12-15

For the SL(2,R) duality-invariant generalization of Maxwell electrodynamics in the presence of both electric and magnetic sources, we formulate a local, manifestly duality-symmetric, Zwanziger-type action by introducing a pair of four-potentials A{sup μ} and B{sup μ} in a judicious way. On the two potentials A{sup μ} and B{sup μ} the SL(2,R) duality transformation acts in a simple linear manner. In quantum theory including charged source fields, this action can be recast as a SL(2,Z)-invariant action. Also given is a Zwanziger-type action for SL(2,R) duality-invariant Born–Infeld electrodynamics which can be important for D-brane dynamics in string theory. -- Highlights: •We formulatemore » a local, manifestly duality-symmetric, Zwanziger-type action. •Maxwell electrodynamics is generalized to include dilaton and axion fields. •SL(2,R) symmetry is manifest. •We formulate a local, manifestly duality-symmetric, nonlinear Born–Infeld action with SL(2,R) symmetry.« less

Corrective Action Decision Document for Corrective Action Unit 204: Storage Bunkers, Nevada Test Site, Nevada: Revision 0, Including Errata Sheet

DOE Office of Scientific and Technical Information (OSTI.GOV)

U.S. Department of Energy, National Nuclear Security Administration Nevada Site Office

2004-04-01

This Corrective Action Decision Document identifies the U.S. Department of Energy, National Nuclear Security Administration Nevada Site Office's corrective action alternative recommendation for each of the corrective action sites (CASs) within Corrective Action Unit (CAU) 204: Storage Bunkers, Nevada Test Site (NTS), Nevada, under the Federal Facility Agreement and Consent Order. An evaluation of analytical data from the corrective action investigation, review of current and future operations at each CAS, and a detailed comparative analysis of potential corrective action alternatives were used to determine the appropriate corrective action for each CAS. There are six CASs in CAU 204, which aremore » all located between Areas 1, 2, 3, and 5 on the NTS. The No Further Action alternative was recommended for CASs 01-34-01, 02-34-01, 03-34-01, and 05-99-02; and a Closure in Place with Administrative Controls recommendation was the preferred corrective action for CASs 05-18-02 and 05-33-01. These alternatives were judged to meet all requirements for the technical components evaluated as well as applicable state and federal regulations for closure of the sites and will eliminate potential future exposure pathways to the contaminated media at CAU 204.« less

How Neurons Work: An Analogy & Demonstration Using a Sparkler & a Frying Pan

ERIC Educational Resources Information Center

Griff, Edwin R.

2006-01-01

Information in the nervous system is conveyed by impulses called action potentials: large, transient electrochemical changes in a neuron's membrane. Though action potentials are a basic feature of neurons, teachers often have trouble explaining this neurophysiological concept, and students have difficulty understanding it. While easy-to-understand…

Computer Simulation of the Neuronal Action Potential.

ERIC Educational Resources Information Center

Solomon, Paul R.; And Others

1988-01-01

A series of computer simulations of the neuronal resting and action potentials are described. Discusses the use of simulations to overcome the difficulties of traditional instruction, such as blackboard illustration, which can only illustrate these events at one point in time. Describes systems requirements necessary to run the simulations.…

The Belem Framework for Action: Harnessing the Power and Potential of Adult Learning and Education for a Viable Future

ERIC Educational Resources Information Center

Adult Learning, 2012

2012-01-01

This article presents the Belem Framework for Action. This framework focuses on harnessing the power and potential of adult learning and education for a viable future. This framework begins with a preamble on adult education and towards lifelong learning.

Introducing the Action Potential to Psychology Students

ERIC Educational Resources Information Center

Simon-Dack, Stephanie L.

2014-01-01

For this simple active learning technique for teaching, students are assigned "roles" and act out the process of the action potential (AP), including the firing threshold, ion-specific channels for ions to enter and leave the cell, diffusion, and the refractory period. Pre-post test results indicated that students demonstrated increased…

7 CFR 624.4 - Definitions.

Code of Federal Regulations, 2010 CFR

2010-01-01

... occurrence that could cause significant damage to property or threaten human life in the near future. (e)(1...) Exigency means those situations that demand immediate action to avoid potential loss of life or property..., cause new damages or the potential loss of life if action to remedy the situation is not taken...

7 CFR 624.4 - Definitions.

Code of Federal Regulations, 2011 CFR

2011-01-01

... occurrence that could cause significant damage to property or threaten human life in the near future. (e)(1...) Exigency means those situations that demand immediate action to avoid potential loss of life or property..., cause new damages or the potential loss of life if action to remedy the situation is not taken...

Home Interactive Media: An Analysis of Potential Abusers of Privacy.

ERIC Educational Resources Information Center

Wegner, John M.

1985-01-01

Examines potential threats to privacy posed by development of unified interaction systems in the home. Applicability of existing federal laws, constitutional provisions, and regulatory actions, and the possible technical and legislative actions that may be useful in curtailing possible privacy abuses in these systems are analyzed. (Author/MBR)

14 CFR § 1216.306 - Actions normally requiring an EIS.

Code of Federal Regulations, 2014 CFR

2014-01-01

...) § 1216.306 Actions normally requiring an EIS. (a) NASA will prepare an EIS for actions with the potential...) Typical NASA actions normally requiring an EIS include: (1) Development and operation of new launch... using a total quantity of radioactive material greater than the quantity for which the NASA Nuclear...

Motor resonance facilitates movement execution: an ERP and kinematic study

PubMed Central

Ménoret, Mathilde; Curie, Aurore; des Portes, Vincent; Nazir, Tatjana A.; Paulignan, Yves

2013-01-01

Action observation, simulation and execution share neural mechanisms that allow for a common motor representation. It is known that when these overlapping mechanisms are simultaneously activated by action observation and execution, motor performance is influenced by observation and vice versa. To understand the neural dynamics underlying this influence and to measure how variations in brain activity impact the precise kinematics of motor behavior, we coupled kinematics and electrophysiological recordings of participants while they performed and observed congruent or non-congruent actions or during action execution alone. We found that movement velocities and the trajectory deviations of the executed actions increased during the observation of congruent actions compared to the observation of non-congruent actions or action execution alone. This facilitation was also discernible in the motor-related potentials of the participants; the motor-related potentials were transiently more negative in the congruent condition around the onset of the executed movement, which occurred 300 ms after the onset of the observed movement. This facilitation seemed to depend not only on spatial congruency but also on the optimal temporal relationship of the observation and execution events. PMID:24133437

Environmental Assessment, Project MOUNTAINVIEW Facility, Buckley Air Force Base, Colorado

DTIC Science & Technology

2011-10-01

Overall, construction and demolition activities would have the potential to result in adverse effects on surface water quality, but the development of a ... Studied in Detail This EA examines potential effects of the Proposed Action and No Action Alternative on 10 resource areas: noise, land use, air...not in a floodplain. Any potential indirect effects on floodplains would be addressed through the use of storm water best management practices

The energetics of central nervous system white matter

PubMed Central

Harris, Julia J.; Attwell, David

2012-01-01

The energetics of CNS white matter are poorly understood. We derive a signalling energy budget for rodent white matter (based on data from the optic nerve and corpus callosum) which can be compared to previous energy budgets for the grey matter regions of the brain, perform a cost-benefit analysis of the energetics of myelination, and assess mechanisms for energy production and glucose supply in myelinated axons. We show that white matter synapses consume ≤0.5% of the energy of grey matter synapses and that this, rather than more energy-efficient action potentials, is the main reason why CNS white matter uses less energy than grey matter. Surprisingly, while the energetic cost of building myelin could be repaid within months by the reduced ATP cost of neuronal action potentials, the energetic cost of maintaining the oligodendrocyte resting potential usually outweighs the saving on action potentials. Thus, although it dramatically speeds action potential propagation, myelination need not save energy. Finally, we show that mitochondria in optic nerve axons could sustain measured firing rates with a plausible density of glucose transporters in the nodal membrane, without the need for energy transfer from oligodendrocytes. PMID:22219296

Immunoglobulinfree light chains reduce in an antigen-specific manner the rate of rise of action potentials of mouse non-nociceptive dorsal root ganglion neurons.

PubMed

Rijnierse, Anneke; Kraneveld, Aletta D; Salemi, Arezo; Zwaneveld, Sandra; Goumans, Aleida P H; Rychter, Jakub W; Thio, Marco; Redegeld, Frank A; Westerink, Remco H S; Kroese, Alfons B A

2013-11-15

Plasma B cells secrete immunoglobulinfree light chains (IgLC) which by binding to mast cells can mediate hypersensitivity responses and are involved in several immunological disorders. To investigate the effects of antigen-specific IgLC activation, intracellular recordings were made from cultured murine dorsal root ganglion (DRG) neurons, which can specifically bind IgLC. The neurons were sensitized with IgLC for 90min and subsequently activated by application of the corresponding antigen (DNP-HSA). Antigen application induced a decrease in the rate of rise of the action potentials of non-nociceptive neurons (MANOVA, p=2.10(-6)), without affecting the resting membrane potential or firing threshold. The action potentials of the nociceptive neurons (p=0.57) and the electrical excitability of both types of neurons (p>0.35) were not affected. We conclude that IgLC can mediate antigen-specific responses by reducing the rate of rise of action potentials in non-nociceptive murine DRG neurons. We suggest that antigen-specific activation of IgLC-sensitized non-nociceptive DRG neurons may contribute to immunological hypersensitivity responses and neuroinflammation. © 2013.

Heteromeric Kv7.2/7.3 channels differentially regulate action potential initiation and conduction in neocortical myelinated axons.

PubMed

Battefeld, Arne; Tran, Baouyen T; Gavrilis, Jason; Cooper, Edward C; Kole, Maarten H P

2014-03-05

Rapid energy-efficient signaling along vertebrate axons is achieved through intricate subcellular arrangements of voltage-gated ion channels and myelination. One recently appreciated example is the tight colocalization of K(v)7 potassium channels and voltage-gated sodium (Na(v)) channels in the axonal initial segment and nodes of Ranvier. The local biophysical properties of these K(v)7 channels and the functional impact of colocalization with Na(v) channels remain poorly understood. Here, we quantitatively examined K(v)7 channels in myelinated axons of rat neocortical pyramidal neurons using high-resolution confocal imaging and patch-clamp recording. K(v)7.2 and 7.3 immunoreactivity steeply increased within the distal two-thirds of the axon initial segment and was mirrored by the conductance density estimates, which increased from ~12 (proximal) to 150 pS μm(-2) (distal). The axonal initial segment and nodal M-currents were similar in voltage dependence and kinetics, carried by K(v)7.2/7.3 heterotetramers, 4% activated at the resting membrane potential and rapidly activated with single-exponential time constants (~15 ms at 28 mV). Experiments and computational modeling showed that while somatodendritic K(v)7 channels are strongly activated by the backpropagating action potential to attenuate the afterdepolarization and repetitive firing, axonal K(v)7 channels are minimally recruited by the forward-propagating action potential. Instead, in nodal domains K(v)7.2/7.3 channels were found to increase Na(v) channel availability and action potential amplitude by stabilizing the resting membrane potential. Thus, K(v)7 clustering near axonal Na(v) channels serves specific and context-dependent roles, both restraining initiation and enhancing conduction of the action potential.

Heteromeric Kv7.2/7.3 Channels Differentially Regulate Action Potential Initiation and Conduction in Neocortical Myelinated Axons

PubMed Central

Battefeld, Arne; Tran, Baouyen T.; Gavrilis, Jason; Cooper, Edward C.

2014-01-01

Rapid energy-efficient signaling along vertebrate axons is achieved through intricate subcellular arrangements of voltage-gated ion channels and myelination. One recently appreciated example is the tight colocalization of Kv7 potassium channels and voltage-gated sodium (Nav) channels in the axonal initial segment and nodes of Ranvier. The local biophysical properties of these Kv7 channels and the functional impact of colocalization with Nav channels remain poorly understood. Here, we quantitatively examined Kv7 channels in myelinated axons of rat neocortical pyramidal neurons using high-resolution confocal imaging and patch-clamp recording. Kv7.2 and 7.3 immunoreactivity steeply increased within the distal two-thirds of the axon initial segment and was mirrored by the conductance density estimates, which increased from ∼12 (proximal) to 150 pS μm−2 (distal). The axonal initial segment and nodal M-currents were similar in voltage dependence and kinetics, carried by Kv7.2/7.3 heterotetramers, 4% activated at the resting membrane potential and rapidly activated with single-exponential time constants (∼15 ms at 28 mV). Experiments and computational modeling showed that while somatodendritic Kv7 channels are strongly activated by the backpropagating action potential to attenuate the afterdepolarization and repetitive firing, axonal Kv7 channels are minimally recruited by the forward-propagating action potential. Instead, in nodal domains Kv7.2/7.3 channels were found to increase Nav channel availability and action potential amplitude by stabilizing the resting membrane potential. Thus, Kv7 clustering near axonal Nav channels serves specific and context-dependent roles, both restraining initiation and enhancing conduction of the action potential. PMID:24599470

Corrective Action Investigation Plan for Corrective Action Unit 528: Polychlorinated Biphenyls Contamination, Nevada Test Site, Nevada, Rev. 0

DOE Office of Scientific and Technical Information (OSTI.GOV)

U.S. Department of Energy, National Nuclear Security Administration Nevada Site Office

This Corrective Action Investigation Plan contains the U.S. Department of Energy, National Nuclear Security Administration Nevada Site Office's approach to collect the data necessary to evaluate corrective action alternatives appropriate for the closure of Corrective Action Unit (CAU) 528, Polychlorinated Biphenyls Contamination (PCBs), Nevada Test Site (NTS), Nevada, under the Federal Facility Agreement and Consent Order. Located in the southwestern portion of Area 25 on the NTS in Jackass Flats (adjacent to Test Cell C [TCC]), CAU 528 consists of Corrective Action Site 25-27-03, Polychlorinated Biphenyls Surface Contamination. Test Cell C was built to support the Nuclear Rocket Development Stationmore » (operational between 1959 and 1973) activities including conducting ground tests and static firings of nuclear engine reactors. Although CAU 528 was not considered as a direct potential source of PCBs and petroleum contamination, two potential sources of contamination have nevertheless been identified from an unknown source in concentrations that could potentially pose an unacceptable risk to human health and/or the environment. This CAU's close proximity to TCC prompted Shaw to collect surface soil samples, which have indicated the presence of PCBs extending throughout the area to the north, east, south, and even to the edge of the western boundary. Based on this information, more extensive field investigation activities are being planned, the results of which are to be used to support a defensible evaluation of corrective action alternatives in the corrective action decision document.« less

Identifying key genes, pathways and screening therapeutic agents for manganese-induced Alzheimer disease using bioinformatics analysis.

PubMed

Ling, JunJun; Yang, Shengyou; Huang, Yi; Wei, Dongfeng; Cheng, Weidong

2018-06-01

Alzheimer disease (AD) is a progressive neurodegenerative disease, the etiology of which remains largely unknown. Accumulating evidence indicates that elevated manganese (Mn) in brain exerts toxic effects on neurons and contributes to AD development. Thus, we aimed to explore the gene and pathway variations through analysis of high through-put data in this process.To screen the differentially expressed genes (DEGs) that may play critical roles in Mn-induced AD, public microarray data regarding Mn-treated neurocytes versus controls (GSE70845), and AD versus controls (GSE48350), were downloaded and the DEGs were screened out, respectively. The intersection of the DEGs of each datasets was obtained by using Venn analysis. Then, gene ontology (GO) function analysis and KEGG pathway analysis were carried out. For screening hub genes, protein-protein interaction network was constructed. At last, DEGs were analyzed in Connectivity Map (CMAP) for identification of small molecules that overcome Mn-induced neurotoxicity or AD development.The intersection of the DEGs obtained 140 upregulated and 267 downregulated genes. The top 5 items of biological processes of GO analysis were taxis, chemotaxis, cell-cell signaling, regulation of cellular physiological process, and response to wounding. The top 5 items of KEGG pathway analysis were cytokine-cytokine receptor interaction, apoptosis, oxidative phosphorylation, Toll-like receptor signaling pathway, and insulin signaling pathway. Afterwards, several hub genes such as INSR, VEGFA, PRKACB, DLG4, and BCL2 that might play key roles in Mn-induced AD were further screened out. Interestingly, tyrphostin AG-825, an inhibitor of tyrosine phosphorylation, was predicted to be a potential agent for overcoming Mn-induced neurotoxicity or AD development.The present study provided a novel insight into the molecular mechanisms of Mn-induced neurotoxicity or AD development and screened out several small molecular candidates that might be critical for Mn neurotoxicity prevention and Mn-induced AD treatment.

Ionic channels underlying the ventricular action potential in zebrafish embryo.

PubMed

Alday, Aintzane; Alonso, Hiart; Gallego, Monica; Urrutia, Janire; Letamendia, Ainhoa; Callol, Carles; Casis, Oscar

2014-06-01

Over the last years zebrafish has become a popular model in the study of cardiac physiology, pathology and pharmacology. Recently, the application of the 3Rs regulation and the characteristics of the embryo have reduced the use of adult zebrafish use in many studies. However, the zebrafish embryo cardiac physiology is poorly characterized since most works have used indirect techniques and direct recordings of cardiac action potential and ionic currents are scarce. In order to optimize the zebrafish embryo model, we used electrophysiological, pharmacological and immunofluorescence tools to identify the characteristics and the ionic channels involved in the ventricular action potentials of zebrafish embryos. The application of Na(+) or T-type Ca(+2) channel blockers eliminated the cardiac electrical activity, indicating that the action potential upstroke depends on Na(+) and T-type Ca(+2) currents. The plateau phase depends on L-type Ca(+2) channels since it is abolished by specific blockade. The direct channel blockade indicates that the action potential repolarization and diastolic potential depends on ERG K(+) channels. The presence in the embryonic heart of the Nav1.5, Cav1.2, Cav3.2 and ERG channels was also confirmed by immunofluorescence, while the absence of effect of specific blockers and immunostaining indicate that two K(+) repolarizing currents present in human heart, Ito and IKs, are absent in the embryonic zebrafish heart. Our results describe the ionic channels present and its role in the zebrafish embryo heart and support the use of zebrafish embryos to study human diseases and their use for drug testing. Copyright © 2014 Elsevier Ltd. All rights reserved.

The action of chlorphenesin carbamate on the frog spinal cord.

PubMed

Aihara, H; Kurachi, M; Nakane, S; Sasajima, M; Ohzeki, M

1980-02-01

Studies were carried out to elucidate the mechanism of action of chlorphenesin carbamate (CPC) and to compare the effect of the drug with that of mephenesin on the isolated bullfrog spinal cord. Ventral and dorsal root potentials were recorded by means of the sucrose-gap method. CPC caused marked hyperpolarizations and depressed spontaneous activities in both of the primary afferent terminals (PAT) and motoneurons (MN). These hyperpolarizations were observed even in high-Mg2+ and Ca2+-free Ringer's solution, suggesting that CPC has direct actions on PAT and MN. Various reflex potentials (dorsal and ventral root potentials elicited by stimulating dorsal and ventral root, respectively) tended to be depressed by CPC as well as by mephenesin. Excitatory amino acids (L-aspartic acid and L-glutamic acid) caused marked depolarizations in PAT and MN, and increased the firing rate in MN. CPC did not modify the depolarization but abolished the motoneuron firing induced by these amino acids. However, mephenesin reduced both the depolarization and the motoneuron firing. The dorsal and ventral root potentials evoked by tetanic stimulation (40 Hz) of the dorsal root were depressed by the drugs. These results indicate that CPC has an apparent depressing action on the spinal neuron, and this action may be ascribed to the slight hyperpolarization and/or the prolongation of refractory period.

Ephaptic conduction in a cardiac strand model with 3D electrodiffusion

PubMed Central

Mori, Yoichiro; Fishman, Glenn I.; Peskin, Charles S.

2008-01-01

We study cardiac action potential propagation under severe reduction in gap junction conductance. We use a mathematical model of cellular electrical activity that takes into account both three-dimensional geometry and ionic concentration effects. Certain anatomical and biophysical parameters are varied to see their impact on cardiac action potential conduction velocity. This study uncovers quantitative features of ephaptic propagation that differ from previous studies based on one-dimensional models. We also identify a mode of cardiac action potential propagation in which the ephaptic and gap-junction-mediated mechanisms alternate. Our study demonstrates the usefulness of this modeling approach for electrophysiological systems especially when detailed membrane geometry plays an important role. PMID:18434544

Action prediction based on anticipatory brain potentials during simulated driving

NASA Astrophysics Data System (ADS)

Khaliliardali, Zahra; Chavarriaga, Ricardo; Gheorghe, Lucian Andrei; Millán, José del R.

2015-12-01

Objective. The ability of an automobile to infer the driver’s upcoming actions directly from neural signals could enrich the interaction of the car with its driver. Intelligent vehicles fitted with an on-board brain-computer interface able to decode the driver’s intentions can use this information to improve the driving experience. In this study we investigate the neural signatures of anticipation of specific actions, namely braking and accelerating. Approach. We investigated anticipatory slow cortical potentials in electroencephalogram recorded from 18 healthy participants in a driving simulator using a variant of the contingent negative variation (CNV) paradigm with Go and No-go conditions: count-down numbers followed by ‘Start’/‘Stop’ cue. We report decoding performance before the action onset using a quadratic discriminant analysis classifier based on temporal features. Main results. (i) Despite the visual and driving related cognitive distractions, we show the presence of anticipatory event related potentials locked to the stimuli onset similar to the widely reported CNV signal (with an average peak value of -8 μV at electrode Cz). (ii) We demonstrate the discrimination between cases requiring to perform an action upon imperative subsequent stimulus (Go condition, e.g. a ‘Red’ traffic light) versus events that do not require such action (No-go condition; e.g. a ‘Yellow’ light); with an average single trial classification performance of 0.83 ± 0.13 for braking and 0.79 ± 0.12 for accelerating (area under the curve). (iii) We show that the centro-medial anticipatory potentials are observed as early as 320 ± 200 ms before the action with a detection rate of 0.77 ± 0.12 in offline analysis. Significance. We show for the first time the feasibility of predicting the driver’s intention through decoding anticipatory related potentials during simulated car driving with high recognition rates.

The pH-dependent local anesthetic activity of diethylaminoethanol, a procaine metabolite.

PubMed

Butterworth, J F; Lief, P A; Strichartz, G R

1988-04-01

To test whether the products of procaine hydrolysis have local anesthetic actions resembling those of procaine, the authors compared the ability of procaine and its metabolites diethylaminoethanol (DEAE) and para-aminobenzoic acid (PABA) to block compound action potentials in excised, desheathed frog and rat sciatic nerves. Studies were performed in solutions of impermeant buffers at pH 7.4 (corresponding to mammalian physiologic pH) and at pH 9.2 (close to the pKa of procaine and DEAE) to test for extracellular pH-dependent increases in drug permeation and potency. Both procaine and DEAE inhibited compound action potentials at pH 7.4 and 9.2 in a reversible and dose-dependent manner, and both were approximately ten-fold more potent at pH 9.2 than at pH 7.4, procaine inhibiting the action potential height by 50% at 0.15 mM (pH 9.2) and 1.1 mM (pH 7.4), DEAE at 4 mM (pH 9.2) and 70 mM (pH 7.4). In contrast, PABA at concentrations up to 25 mM and at either pH failed to inhibit compound action potentials, and did not modify the effects of DEAE when both drugs were given together. Procaine produced greater use-dependent block at the higher pH and at higher stimulation rates (100 Hz vs. 40 Hz); DEAE produced almost no use-dependent block. These observations suggest: 1) that DEAE might account for some of the neuropharmacologic activity of procaine in techniques that favor the accumulation of metabolites (such as those requiring large doses or prolonged infusions); and 2) that alkalinization of procaine and DEAE solutions appears to increase their potency for both resting and use-dependent block of action potentials.

40 CFR 6.100 - Policy and purpose.

Code of Federal Regulations, 2010 CFR

2010-07-01

... ENVIRONMENTAL POLICY ACT AND ASSESSING THE ENVIRONMENTAL EFFECTS ABROAD OF EPA ACTIONS General Provisions for... processes appropriate and careful consideration of all environmental effects of proposed actions, analyze potential environmental effects of proposed actions and their alternatives for public understanding and...

Not so secret agents: Event-related potentials to semantic roles in visual event comprehension.

PubMed

Cohn, Neil; Paczynski, Martin; Kutas, Marta

2017-12-01

Research across domains has suggested that agents, the doers of actions, have a processing advantage over patients, the receivers of actions. We hypothesized that agents as "event builders" for discrete actions (e.g., throwing a ball, punching) build on cues embedded in their preparatory postures (e.g., reaching back an arm to throw or punch) that lead to (predictable) culminating actions, and that these cues afford frontloading of event structure processing. To test this hypothesis, we compared event-related brain potentials (ERPs) to averbal comic panels depicting preparatory agents (ex. reaching back an arm to punch) that cued specific actions with those to non-preparatory agents (ex. arm to the side) and patients that did not cue any specific actions. We also compared subsequent completed action panels (ex. agent punching patient) across conditions, where we expected an inverse pattern of ERPs indexing the differential costs of processing completed actions asa function of preparatory cues. Preparatory agents evoked a greater frontal positivity (600-900ms) relative to non-preparatory agents and patients, while subsequent completed actions panels following non-preparatory agents elicited a smaller frontal positivity (600-900ms). These results suggest that preparatory (vs. non-) postures may differentially impact the processing of agents and subsequent actions in real time. Copyright © 2017 Elsevier Inc. All rights reserved.

Passive Responses Resembling Action Potentials: A Device for the Classroom

ERIC Educational Resources Information Center

Newman, Ian A.; Pickard, Barbara G.

1975-01-01

Describes the construction and operation of a network of entirely passive electrical components that gives a response to an electrical shock similar to an action potential. The network of resistors, capacitors, and diodes was developed to produce responses that would mimic those observed, for example, when a dark-grown pea epicotyl is shocked…

The Transformative Potential of Action Research and ICT in the Second Language (L2) Classroom

ERIC Educational Resources Information Center

Farren, Margaret; Crotty, Yvonne; Kilboy, Laura

2015-01-01

This study shows the transformative potential of action research and information and communications technology (ICT) in the second language (L2) classroom. Two enquiries from teacher-researchers are detailed in the article. Their engagement in a collaborative professional development Masters programme was pivotal in designing and implementing ICT…

37 CFR 2.117 - Suspension of proceedings.

Code of Federal Regulations, 2011 CFR

2011-07-01

... Board that a party or parties to a pending case are engaged in a civil action or another Board... termination of the civil action or the other Board proceeding. (b) Whenever there is pending before the Board both a motion to suspend and a motion which is potentially dispositive of the case, the potentially...

37 CFR 2.117 - Suspension of proceedings.

Code of Federal Regulations, 2010 CFR

2010-07-01

... Board that a party or parties to a pending case are engaged in a civil action or another Board... termination of the civil action or the other Board proceeding. (b) Whenever there is pending before the Board both a motion to suspend and a motion which is potentially dispositive of the case, the potentially...

Microelectrode array measurement of potassium ion channel remodeling on the field action potential duration in rapid atrial pacing rabbits model.

PubMed

Sun, Juan; Yan, Huang; Wugeti, Najina; Guo, Yujun; Zhang, Ling; Ma, Mei; Guo, Xingui; Jiao, Changan; Xu, Wenli; Li, Tianqi

2015-01-01

Atrial fibrillation (AF) arises from abnormalities in atrial structure and electrical activity. Microelectrode arrays (MEA) is a real-time, nondestructive measurement of the resting and action potential signal, from myocardial cells, to the peripheral circuit of electrophysiological activity. This study examined the field action potential duration (fAPD) of the right atrial appendage (RAA) by MEA in rapid atrial pacing (RAP) in the right atrium of rabbits. In addition, this study also investigated the effect of potassium ion channel blockers on fAPD. 40 New Zealand white rabbits of either sex were randomly divided into 3 groups: 1) the control, 2) potassium ion channel blocker (TEA, 4-Ap and BaCl2), and 3) amiodarone groups. The hearts were quickly removed and right atrial appendage sectioned (slice thickness 500 μm). Each slice was perfused with Tyrode's solution and continuously stimulated for 30 minutes. Sections from the control group were superfused with Tyrode's solution for 10 minutes, while the blocker groups and amiodarone were both treated with their respective compounds for 10 minutes each. The fAPD of RAA and action field action potential morphology were measured using MEA. In non-pace (control) groups, fAPD was 188.33 ± 18.29 ms after Tyrode's solution superfusion, and 173.91 ± 6.83 ms after RAP. In pace/potassium ion channel groups, TEA and BaCl2 superfusion prolonged atrial field action potential (fAPD) (control vs blocker: 176.67 ± 8.66 ms vs 196.11 ± 10.76 ms, 182.22 ± 12.87 ms vs 191.11 ± 13.09 ms with TEA and BaCl2 superfusion, respectively, P < 0.05). 4-AP superfusion significantly prolonged FAPD. In pace/amiodarone groups, 4-Ap superfusion extended fAPD. MEA was a sensitive and stable reporter for the measurement of the tissue action potential in animal heart slices. After superfusing potassium ion channel blockers, fAPD was prolonged. These results suggest that Ito, IKur and IK1 remodel and mediate RAP-induced atrial electrical remodeling. Amiodarone alter potassium ion channel activity (Ito, IKur, IK1 and IKs), shortening fAPD.

Duration of the distal compound muscle action potential for diagnosis of chronic inflammatory demyelinating polyneuropathy: effects of low-cut filters.

PubMed

Isose, Sagiri; Misawa, Sonoko; Sonoo, Masahiro; Shimuzu, Toshio; Oishi, Chizuko; Shibuya, Kazumoto; Nasu, Saiko; Sekiguchi, Yukari; Mitsuma, Satsuki; Beppu, Minako; Omori, Shigeki; Komori, Tetsuo; Kokubun, Norito; Inaba, Akira; Hirashima, Fumiko; Kuwabara, Satoshi

2014-10-01

In current electrodiagnostic criteria for chronic inflammatory demyelinating polyneuropathy, the cutoff values of distal compound muscle action potential (DCMAP) duration are defined using electromyogram low-cut filter setting of 20 Hz. We aimed to assess effects of low-cut filter on DCMAP duration (10 vs. 20 Hz). We prospectively measured DCMAP duration in 130 normal controls and 42 patients, fulfilling diagnostic criteria for typical chronic inflammatory demyelinating polyneuropathy by European Federation of Neurological Societies/Peripheral Nerve Society. Distal compound muscle action potential duration was significantly shortened with 20-Hz than 10-Hz filtering. When the cutoff values were defined as the upper limit of normal (ULN, mean + 2.5SD), the sensitivity/specificity was 67%/95% in 10-Hz recordings, and 69%/95% in 20-Hz recordings. This diagnostic accuracy was similar to that defined by receiver operating characteristic analyses. Distal compound muscle action potential duration significantly affected by the low-cut electromyogram filter setting, but with at least 10 and 20 Hz, the diagnostic accuracy is similar.

Human Nav1.8: enhanced persistent and ramp currents contribute to distinct firing properties of human DRG neurons

PubMed Central

Han, Chongyang; Estacion, Mark; Huang, Jianying; Vasylyev, Dymtro; Zhao, Peng; Dib-Hajj, Sulayman D.

2015-01-01

Although species-specific differences in ion channel properties are well-documented, little has been known about the properties of the human Nav1.8 channel, an important contributor to pain signaling. Here we show, using techniques that include voltage clamp, current clamp, and dynamic clamp in dorsal root ganglion (DRG) neurons, that human Nav1.8 channels display slower inactivation kinetics and produce larger persistent current and ramp current than previously reported in other species. DRG neurons expressing human Nav1.8 channels unexpectedly produce significantly longer-lasting action potentials, including action potentials with half-widths in some cells >10 ms, and increased firing frequency compared with the narrower and usually single action potentials generated by DRG neurons expressing rat Nav1.8 channels. We also show that native human DRG neurons recapitulate these properties of Nav1.8 current and the long-lasting action potentials. Together, our results demonstrate strikingly distinct properties of human Nav1.8, which contribute to the firing properties of human DRG neurons. PMID:25787950

Human Na(v)1.8: enhanced persistent and ramp currents contribute to distinct firing properties of human DRG neurons.

PubMed

Han, Chongyang; Estacion, Mark; Huang, Jianying; Vasylyev, Dymtro; Zhao, Peng; Dib-Hajj, Sulayman D; Waxman, Stephen G

2015-05-01

Although species-specific differences in ion channel properties are well-documented, little has been known about the properties of the human Nav1.8 channel, an important contributor to pain signaling. Here we show, using techniques that include voltage clamp, current clamp, and dynamic clamp in dorsal root ganglion (DRG) neurons, that human Na(v)1.8 channels display slower inactivation kinetics and produce larger persistent current and ramp current than previously reported in other species. DRG neurons expressing human Na(v)1.8 channels unexpectedly produce significantly longer-lasting action potentials, including action potentials with half-widths in some cells >10 ms, and increased firing frequency compared with the narrower and usually single action potentials generated by DRG neurons expressing rat Na(v)1.8 channels. We also show that native human DRG neurons recapitulate these properties of Na(v)1.8 current and the long-lasting action potentials. Together, our results demonstrate strikingly distinct properties of human Na(v)1.8, which contribute to the firing properties of human DRG neurons.

Semantic priming in the motor cortex: evidence from combined repetitive transcranial magnetic stimulation and event-related potential.

PubMed

Kuipers, Jan-Rouke; van Koningsbruggen, Martijn; Thierry, Guillaume

2013-08-21

Reading action verbs is associated with activity in the motor cortices involved in performing the corresponding actions. Here, we present new evidence that the motor cortex is involved in semantic processing of bodily action verbs. In contrast to previous studies, we used a direct, nonbehavioural index of semantic processing after repetitive transcranial magnetic stimulation (rTMS). Participants saw pairs of hand-related (e.g. to grab-to point) or mouth-related (e.g. to speak-to sing) verbs, whereas semantic priming was assessed using event-related potentials. Presentation of the first verb coincided with rTMS over the participant's cortical-left hand area and event-related brain potentials were analysed time-locked to the presentation onset of the second verb. Semantic integration - indexed by the N400 brain potential - was impaired for hand-related but not for mouth-related verb pairs after rTMS. This finding provides strong evidence that the motor cortex is involved in semantic encoding of action verbs, and supports the 'embodied semantics' hypothesis.

Issues in Action Learning: A Critical Realist Interpretation

ERIC Educational Resources Information Center

Burgoyne, John

2009-01-01

The purpose of this paper is to argue that the perspective of "critical realism" has considerable potential for moving forward the theory and practice of action learning. The paper addresses three questions: (1) Does action learning emphasise the individual or the collective? (2) Can action learning be thought of as critical, but should it also be…

40 CFR 147.2914 - Corrective action for wells authorized by rule.

Code of Federal Regulations, 2010 CFR

2010-07-01

... potential endangerment of an USDW, then action as described in paragraph (a) (1) or (2) of this section must... 40 Protection of Environment 22 2010-07-01 2010-07-01 false Corrective action for wells authorized... PROGRAMS Osage Mineral Reserve-Class II Wells § 147.2914 Corrective action for wells authorized by rule...

Persistence and Graduation of UC Davis Undergraduates Admitted by Special Action: 1975-1985.

ERIC Educational Resources Information Center

Hunziker, Celeste M.

Persistence and graduation rates of University of California, Davis, special action students admitted in any fall quarter from 1975 to 1985 were studied. Special action students show academic potential but do not meet admission requirements of completed course work and academic achievement. The number of special action students during this 10-year…

75 FR 29431 - Coat Protein of Plum Pox Virus; Exemption from the Requirement of a Tolerance

Federal Register 2010, 2011, 2012, 2013, 2014

2010-05-26

... (EPA). ACTION: Final rule. SUMMARY: This regulation establishes an exemption from the requirement of a... SUPPLEMENTARY INFORMATION). ADDRESSES: EPA has established a docket for this action under docket identification... A. Does this Action Apply to Me? You may be potentially affected by this action if you are an...

Agent based modeling in tactical wargaming

NASA Astrophysics Data System (ADS)

James, Alex; Hanratty, Timothy P.; Tuttle, Daniel C.; Coles, John B.

2016-05-01

Army staffs at division, brigade, and battalion levels often plan for contingency operations. As such, analysts consider the impact and potential consequences of actions taken. The Army Military Decision-Making Process (MDMP) dictates identification and evaluation of possible enemy courses of action; however, non-state actors often do not exhibit the same level and consistency of planned actions that the MDMP was originally designed to anticipate. The fourth MDMP step is a particular challenge, wargaming courses of action within the context of complex social-cultural behaviors. Agent-based Modeling (ABM) and its resulting emergent behavior is a potential solution to model terrain in terms of the human domain and improve the results and rigor of the traditional wargaming process.

Estimating the National Carbon Abatement Potential of City Policies: A Data-Driven Approach

DOE Office of Scientific and Technical Information (OSTI.GOV)

O'Shaughnessy, Eric; Heeter, Jenny; Keyser, David

Cities are increasingly taking actions such as building code enforcement, urban planning, and public transit expansion to reduce emissions of carbon dioxide in their communities and municipal operations. However, many cities lack the quantitative information needed to estimate policy impacts and prioritize city actions in terms of carbon abatement potential and cost effectiveness. This report fills this research gap by providing methodologies to assess the carbon abatement potential of a variety of city actions. The methodologies are applied to an energy use data set of 23,458 cities compiled for the U.S. Department of Energy City Energy Profile tool. The analysismore » develops a national estimate of the carbon abatement potential of realizable city actions in six specific policy areas encompassing the most commonly implemented city actions. The results of this analysis suggest that, in aggregate, cities could reduce nationwide carbon emissions by about 210 million metric tons of carbon dioxide (MMT CO2) per year in a 'moderate abatement scenario' by 2035 and 480 MMT CO2/year in a 'high abatement scenario' by 2035 through these common actions typically within a city's control in the six policy areas. The aggregate carbon abatement potential of these specific areas equates to a reduction of 3%-7% relative to 2013 U.S. emissions. At the city level, the results suggest the average city could reduce carbon emissions by 7% (moderate) to 19% (high) relative to current city-level emissions. In the context of U.S. climate commitments under the 21st session of the Conference of the Parties (COP21), the estimated national abatement potential of the city actions analyzed in this report equates to about 15%-35% of the remaining carbon abatement necessary to achieve the U.S. COP21 target. Additional city actions outside the scope of this report, such as community choice aggregation (city-level purchasing of renewable energy), zero energy districts, and multi-level governance strategies, could significantly augment the carbon abatement contributions of city actions toward national climate targets. The results suggest that cities may play a pivotal role in progress toward national climate targets. In addition to providing carbon and emissions estimates, this report estimates the national net economic impacts of policies for which cost and benefit data are available. Impact metrics include employment, worker earnings, and gross domestic product (GDP). For the policy areas studied, the economic analysis demonstrates that city carbon abatement may be achieved with only minimal and generally slightly positive economic impacts. Employment impacts range from 0.04% to 0.13% of U.S, employment during implementation and zero to 0.1% thereafter. GDP estimates show net impacts of 0.02% to 0.07% of GDP during implementation and impacts from -0.02% to zero thereafter. This report quantitatively demonstrates the material impact of a limited set of local policy areas on national carbon abatement potential. The magnitude of estimated carbon reductions from city policies, 3%-7% of national emissions by 2035, suggests an important role for city-led actions in reaching U.S. climate goals. Multi-level governance at the city, state, and national levels could augment the carbon abatement potential of city actions and make cities a key component of long-term U.S. climate strategies.« less

[Ion-dependency of the GABA-potentiating effects of benzodiazepine tranquilizers and harmane].

PubMed

Abramets, I I; Komissarov, I V

1984-06-01

Experiments on an isolated spinal cord of 8-15-day-old rats have shown that one of the possible mechanisms of the GABA-potentiating action of the benzodiazepine tranquilizer, chlorodiazepoxide, may be a decrease in the intraneuronal concentration of Ca2+. This is evidenced by the enhancement of the GABA-potentiating action of chlorodiazepoxide under Ca2+ deficiency in the medium and in the presence of the blockers of the voltage-dependent Ca2+ ionic channels--Mn2+ and Co2+, and by the reduction of the effect in question under Ca2+ excess in the medium and in the presence of the K+ channels blockers--tetraethylammonium and 4-aminopyridine. The GABA-potentiating action of harmane is likely to be related to the blockade of the voltage-dependent K+ channels and elevation of the intracellular concentration of Ca2+.

The climate mitigation gap: education and government recommendations miss the most effective individual actions

NASA Astrophysics Data System (ADS)

Wynes, Seth; Nicholas, Kimberly A.

2017-07-01

Current anthropogenic climate change is the result of greenhouse gas accumulation in the atmosphere, which records the aggregation of billions of individual decisions. Here we consider a broad range of individual lifestyle choices and calculate their potential to reduce greenhouse gas emissions in developed countries, based on 148 scenarios from 39 sources. We recommend four widely applicable high-impact (i.e. low emissions) actions with the potential to contribute to systemic change and substantially reduce annual personal emissions: having one fewer child (an average for developed countries of 58.6 tonnes CO2-equivalent (tCO2e) emission reductions per year), living car-free (2.4 tCO2e saved per year), avoiding airplane travel (1.6 tCO2e saved per roundtrip transatlantic flight) and eating a plant-based diet (0.8 tCO2e saved per year). These actions have much greater potential to reduce emissions than commonly promoted strategies like comprehensive recycling (four times less effective than a plant-based diet) or changing household lightbulbs (eight times less). Though adolescents poised to establish lifelong patterns are an important target group for promoting high-impact actions, we find that ten high school science textbooks from Canada largely fail to mention these actions (they account for 4% of their recommended actions), instead focusing on incremental changes with much smaller potential emissions reductions. Government resources on climate change from the EU, USA, Canada, and Australia also focus recommendations on lower-impact actions. We conclude that there are opportunities to improve existing educational and communication structures to promote the most effective emission-reduction strategies and close this mitigation gap.

Activity-dependent modulation of the axonal conduction of action potentials along rat hippocampal mossy fibers.

PubMed

Chida, Kuniaki; Kaneko, Kenya; Fujii, Satoshi; Yamazaki, Yoshihiko

2015-01-01

The axonal conduction of action potentials in the nervous system is generally considered to be a stable signal for the relaying of information, and its dysfunction is involved in impairment of cognitive function. Recent evidence suggests that the conduction properties and excitability of axons are more variable than traditionally thought. To investigate possible changes in the conduction of action potentials along axons in the central nervous system, we recorded action potentials from granule cells that were evoked and conducted antidromically along unmyelinated mossy fibers in the rat hippocampus. To evaluate changes in axons by eliminating any involvement of changes in the somata, two latency values were obtained by stimulating at two different positions and the latency difference between the action potentials was measured. A conditioning electrical stimulus of 20 pulses at 1 Hz increased the latency difference and this effect, which lasted for approximately 30 s, was inhibited by the application of an α-amino-3-hydroxy-5-methylisoxazole-4-propionate (AMPA)/kainate receptor antagonist or a GluK1-containing kainate receptor antagonist, but not by an AMPA receptor-selective antagonist or an N-methyl-d-aspartate receptor antagonist. These results indicated that axonal conduction in mossy fibers is modulated in an activity-dependent manner through the activation of GluK1-containing kainate receptors. These dynamic changes in axonal conduction may contribute to the physiology and pathophysiology of the brain. © 2014 Federation of European Neuroscience Societies and John Wiley & Sons Ltd.

Transmural Ultrasound-based Visualization of Patterns of Action Potential Wave Propagation in Cardiac Tissue

PubMed Central

Luther, Stefan; Singh, Rupinder; Gilmour, Robert F.

2010-01-01

The pattern of action potential propagation during various tachyarrhythmias is strongly suspected to be composed of multiple re-entrant waves, but has never been imaged in detail deep within myocardial tissue. An understanding of the nature and dynamics of these waves is important in the development of appropriate electrical or pharmacological treatments for these pathological conditions. We propose a new imaging modality that uses ultrasound to visualize the patterns of propagation of these waves through the mechanical deformations they induce. The new method would have the distinct advantage of being able to visualize these waves deep within cardiac tissue. In this article, we describe one step that would be necessary in this imaging process—the conversion of these deformations into the action potential induced active stresses that produced them. We demonstrate that, because the active stress induced by an action potential is, to a good approximation, only nonzero along the local fiber direction, the problem in our case is actually overdetermined, allowing us to obtain a complete solution. Use of two- rather than three-dimensional displacement data, noise in these displacements, and/or errors in the measurements of the fiber orientations all produce substantial but acceptable errors in the solution. We conclude that the reconstruction of action potential-induced active stress from the deformation it causes appears possible, and that, therefore, the path is open to the development of the new imaging modality. PMID:20499183

A Quantitative Comparison of the Behavior of Human Ventricular Cardiac Electrophysiology Models in Tissue

PubMed Central

Elshrif, Mohamed M.; Cherry, Elizabeth M.

2014-01-01

Numerical integration of mathematical models of heart cell electrophysiology provides an important computational tool for studying cardiac arrhythmias, but the abundance of available models complicates selecting an appropriate model. We study the behavior of two recently published models of human ventricular action potentials, the Grandi-Pasqualini-Bers (GPB) and the O'Hara-Virág-Varró-Rudy (OVVR) models, and compare the results with four previously published models and with available experimental and clinical data. We find the shapes and durations of action potentials and calcium transients differ between the GPB and OVVR models, as do the magnitudes and rate-dependent properties of transmembrane currents and the calcium transient. Differences also occur in the steady-state and S1–S2 action potential duration and conduction velocity restitution curves, including a maximum conduction velocity for the OVVR model roughly half that of the GPB model and well below clinical values. Between single cells and tissue, both models exhibit differences in properties, including maximum upstroke velocity, action potential amplitude, and minimum diastolic interval. Compared to experimental data, action potential durations for the GPB and OVVR models agree fairly well (although OVVR epicardial action potentials are shorter), but maximum slopes of steady-state restitution curves are smaller. Although studies show alternans in normal hearts, it occurs only in the OVVR model, and only for a narrow range of cycle lengths. We find initiated spiral waves do not progress to sustained breakup for either model. The dominant spiral wave period of the GPB model falls within clinically relevant values for ventricular tachycardia (VT), but for the OVVR model, the dominant period is longer than periods associated with VT. Our results should facilitate choosing a model to match properties of interest in human cardiac tissue and to replicate arrhythmia behavior more closely. Furthermore, by indicating areas where existing models disagree, our findings suggest avenues for further experimental work. PMID:24416228

Paired-pulse facilitation and depression at unitary synapses in rat hippocampus: quantal fluctuation affects subsequent release.

PubMed Central

Debanne, D; Guérineau, N C; Gähwiler, B H; Thompson, S M

1996-01-01

1. Excitatory synaptic transmission between pairs of monosynaptically coupled pyramidal cells was examined in rat hippocampal slice cultures. Action potentials were elicited in single CA3 pyramidal cells impaled with microelectrodes and unitary excitatory postsynaptic currents (EPSCs) were recorded in whole-cell voltage-clamped CA1 or CA3 cells. 2. The amplitude of successive unitary EPSCs in response to single action potentials varied. The amplitude of EPSCs was altered by adenosine or changes in the [Mg2+]/[CA2+] ratio. We conclude that single action potentials triggered the release of multiple quanta of glutamate. 3. When two action potentials were elicited in the presynaptic cell, the amplitude of the second EPSC was inversely related to the amplitude of the first. Paired-pulse facilitation (PPF) was observed when the first EPSC was small, i.e. the second EPSC was larger than the first, whereas paired-pulse depression (PPD) was observed when the first EPSC was large. 4. The number of trials displaying PPD was greater when release probability was increased, and smaller when release probability was decreased. 5. PPD was not postsynaptically mediated because it was unaffected by decreasing ionic flux with 6-cyano-7-nitroquinoxaline-2,3-dione (CNQX) or receptor desensitization with aniracetam. 6. PPF was maximal at an interstimulus interval of 70 ms and recovered within 500 ms. Recovery from PPD occurred within 5 s. 7. We propose that multiple release sites are formed by the axon of a CA3 pyramidal cell and a single postsynaptic CA1 or CA3 cell. PPF is observed if the first action potential fails to release transmitter at most release sites. PPD is observed if the first action potential successfully triggers release at most release sites. 8. Our observations of PPF are consistent with the residual calcium hypothesis. We conclude that PPD results from a decrease in quantal content, perhaps due to short-term depletion of readily releasable vesicles. PMID:9011608

Acute alteration of cardiac ECG, action potential, I{sub Kr} and the human ether-a-go-go-related gene (hERG) K{sup +} channel by PCB 126 and PCB 77

DOE Office of Scientific and Technical Information (OSTI.GOV)

Park, Mi-Hyeong; Park, Won Sun; Jo, Su-Hyun, E-mail: suhyunjo@kangwon.ac.kr

2012-07-01

Polychlorinated biphenyls (PCBs) have been known as serious persistent organic pollutants (POPs), causing developmental delays and motor dysfunction. We have investigated the effects of two PCB congeners, 3,3′,4,4′-tetrachlorobiphenyl (PCB 77) and 3,3′,4,4′,5-pentachlorobiphenyl (PCB 126) on ECG, action potential, and the rapidly activating delayed rectifier K{sup +} current (I{sub Kr}) of guinea pigs' hearts, and hERG K{sup +} current expressed in Xenopus oocytes. PCB 126 shortened the corrected QT interval (QTc) of ECG and decreased the action potential duration at 90% (APD{sub 90}), and 50% of repolarization (APD{sub 50}) (P < 0.05) without changing the action potential duration at 20% (APD{submore » 20}). PCB 77 decreased APD{sub 20} (P < 0.05) without affecting QTc, APD{sub 90}, and APD{sub 50}. The PCB 126 increased the I{sub Kr} in guinea-pig ventricular myocytes held at 36 °C and hERG K{sup +} current amplitude at the end of the voltage steps in voltage-dependent mode (P < 0.05); however, PCB 77 did not change the hERG K{sup +} current amplitude. The PCB 77 increased the diastolic Ca{sup 2+} and decreased Ca{sup 2+} transient amplitude (P < 0.05), however PCB 126 did not change. The results suggest that PCB 126 shortened the QTc and decreased the APD{sub 90} possibly by increasing I{sub Kr}, while PCB 77 decreased the APD{sub 20} possibly by other modulation related with intracellular Ca{sup 2+}. The present data indicate that the environmental toxicants, PCBs, can acutely affect cardiac electrophysiology including ECG, action potential, intracellular Ca{sup 2+}, and channel activity, resulting in toxic effects on the cardiac function in view of the possible accumulation of the PCBs in human body. -- Highlights: ► PCBs are known as serious environmental pollutants and developmental disruptors. ► PCB 126 shortened QT interval of ECG and action potential duration. ► PCB 126 increased human ether-a-go-go-related K{sup +} current and I{sub Kr}. ► PCB 77 decreased action potential duration and increased intracellular Ca{sup 2+} content. ► PCBs acutely change cardiac electrophysiology and rhythmicity.« less

Automatic Imitation of Intransitive Actions

ERIC Educational Resources Information Center

Press, Clare; Bird, Geoffrey; Walsh, Eamonn; Heyes, Cecilia

2008-01-01

Previous research has indicated a potential discontinuity between monkey and human ventral premotor-parietal mirror systems, namely that monkey mirror systems process only transitive (object-directed) actions, whereas human mirror systems may also process intransitive (non-object-directed) actions. The present study investigated this discontinuity…

Inhibition by TRPA1 agonists of compound action potentials in the frog sciatic nerve

DOE Office of Scientific and Technical Information (OSTI.GOV)

Matsushita, Akitomo; Ohtsubo, Sena; Fujita, Tsugumi

Highlights: •TRPA1 agonists inhibited compound action potentials in frog sciatic nerves. •This inhibition was not mediated by TRPA1 channels. •This efficacy was comparable to those of lidocaine and cocaine. •We found for the first time an ability of TRPA1 agonists to inhibit nerve conduction. -- Abstract: Although TRPV1 and TRPM8 agonists (vanilloid capsaicin and menthol, respectively) at high concentrations inhibit action potential conduction, it remains to be unknown whether TRPA1 agonists have a similar action. The present study examined the actions of TRPA1 agonists, cinnamaldehyde (CA) and allyl isothiocyanate (AITC), which differ in chemical structure from each other, on compoundmore » action potentials (CAPs) recorded from the frog sciatic nerve by using the air-gap method. CA and AITC concentration-dependently reduced the peak amplitude of the CAP with the IC{sub 50} values of 1.2 and 1.5 mM, respectively; these activities were resistant to a non-selective TRP antagonist ruthenium red or a selective TRPA1 antagonist HC-030031. The CA and AITC actions were distinct in property; the latter but not former action was delayed in onset and partially reversible, and CA but not AITC increased thresholds to elicit CAPs. A CAP inhibition was seen by hydroxy-α-sanshool (by 60% at 0.05 mM), which activates both TRPA1 and TRPV1 channels, a non-vanilloid TRPV1 agonist piperine (by 20% at 0.07 mM) and tetrahydrolavandulol (where the six-membered ring of menthol is opened; IC{sub 50} = 0.38 mM). It is suggested that TRPA1 agonists as well as TRPV1 and TRPM8 agonists have an ability to inhibit nerve conduction without TRP activation, although their agonists are quite different in chemical structure from each other.« less

The afterhyperpolarizing potential following a train of action potentials is suppressed in an acute epilepsy model in the rat Cornu Ammonis 1 area.

PubMed

Kernig, K; Kirschstein, T; Würdemann, T; Rohde, M; Köhling, R

2012-01-10

In hippocampal Cornu Ammonis 1 (CA1) neurons, a prolonged depolarization evokes a train of action potentials followed by a prominent afterhyperpolarizing potential (AHP), which critically dampens neuronal excitability. Because it is not known whether epileptiform activity alters the AHP and whether any alteration of the AHP is independent of inhibition, we acutely induced epileptiform activity by bath application of the GABA(A) receptor blocker gabazine (5 μM) in the rat hippocampal slice preparation and studied its impact on the AHP using intracellular recordings. Following 10 min of gabazine wash-in, slices started to develop spontaneous epileptiform discharges. This disinhibition was accompanied by a significant shift of the resting membrane potential of CA1 neurons to more depolarized values. Prolonged depolarizations (600 ms) elicited a train of action potentials, the number of which was not different between baseline and gabazine treatment. However, the AHP following the train of action potentials was significantly reduced after 20 min of gabazine treatment. When the induction of epileptiform activity was prevented by co-application of 6-cyano-7-nitroquinoxaline-2,3-dione disodium (CNQX, 10 μM) and D-(-)-2-amino-5-phosphonopentanoic acid (D-AP5, 50 μM) to block α-amino-3-hydroxy-5-methylisoxazolepropionate (AMPA) and N-methyl-d-aspartate (NMDA) receptors, respectively, the AHP was preserved despite of GABA(A) receptor inhibition suggesting that the epileptiform activity was required to suppress the AHP. Moreover, the AHP was also preserved when the slices were treated with the protein kinase blockers H-9 (100 μM) and H-89 (1 μM). These results demonstrate that the AHP following a train of action potentials is rapidly suppressed by acutely induced epileptiform activity due to a phosphorylation process-presumably involving protein kinase A. Copyright © 2011 IBRO. Published by Elsevier Ltd. All rights reserved.

Predicting herbicide mixture effects on multiple algal species using mixture toxicity models.

PubMed

Nagai, Takashi

2017-10-01

The validity of the application of mixture toxicity models, concentration addition and independent action, to a species sensitivity distribution (SSD) for calculation of a multisubstance potentially affected fraction was examined in laboratory experiments. Toxicity assays of herbicide mixtures using 5 species of periphytic algae were conducted. Two mixture experiments were designed: a mixture of 5 herbicides with similar modes of action and a mixture of 5 herbicides with dissimilar modes of action, corresponding to the assumptions of the concentration addition and independent action models, respectively. Experimentally obtained mixture effects on 5 algal species were converted to the fraction of affected (>50% effect on growth rate) species. The predictive ability of the concentration addition and independent action models with direct application to SSD depended on the mode of action of chemicals. That is, prediction was better for the concentration addition model than the independent action model for the mixture of herbicides with similar modes of action. In contrast, prediction was better for the independent action model than the concentration addition model for the mixture of herbicides with dissimilar modes of action. Thus, the concentration addition and independent action models could be applied to SSD in the same manner as for a single-species effect. The present study to validate the application of the concentration addition and independent action models to SSD supports the usefulness of the multisubstance potentially affected fraction as the index of ecological risk. Environ Toxicol Chem 2017;36:2624-2630. © 2017 SETAC. © 2017 SETAC.

Portable Conduction Velocity Experiments Using Earthworms for the College and High School Neuroscience Teaching Laboratory

ERIC Educational Resources Information Center

Shannon, Kyle M.; Gage, Gregory J.; Jankovic, Aleksandra; Wilson, W. Jeffrey; Marzullo, Timothy C.

2014-01-01

The earthworm is ideal for studying action potential conduction velocity in a classroom setting, as its simple linear anatomy allows easy axon length measurements and the worm's sparse coding allows single action potentials to be easily identified. The earthworm has two giant fiber systems (lateral and medial) with different conduction velocities…

Youth Participatory Action Research and Educational Transformation: The Potential of Intertextuality as a Methodological Tool

ERIC Educational Resources Information Center

Bertrand, Melanie

2016-01-01

In this article, Melanie Bertrand explores the potential of using the concept of intertextuality--which captures the way snippets of written or spoken text from one source become incorporated into other sources--in the study and practice of youth participatory action research (YPAR). Though this collective and youth-centered form of research…

Rigid and flexible organic electrochemical transistor arrays for monitoring action potentials from electrogenic cells.

PubMed

Yao, Chunlei; Li, Qianqian; Guo, Jing; Yan, Feng; Hsing, I-Ming

2015-03-11

Rigid and flexible organic electrochemical transistor arrays are successfully implemented for monitoring cardiac action potentials. Excellent signal to noise ratios are achieved with values routinely larger than 4. These devices are promising to be used in both conventional and emerging areas. © 2014 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

Viewing Objects and Planning Actions: On the Potentiation of Grasping Behaviours by Visual Objects

ERIC Educational Resources Information Center

Makris, Stergios; Hadar, Aviad A.; Yarrow, Kielan

2011-01-01

How do humans interact with tools? Gibson (1979) suggested that humans perceive directly what tools afford in terms of meaningful actions. This "affordances" hypothesis implies that visual objects can potentiate motor responses even in the absence of an intention to act. Here we explore the temporal evolution of motor plans afforded by common…

Modeling the attenuation and failure of action potentials in the dendrites of hippocampal neurons.

PubMed Central

Migliore, M

1996-01-01

We modeled two different mechanisms, a shunting conductance and a slow sodium inactivation, to test whether they could modulate the active propagation of a train of action potentials in a dendritic tree. Computer simulations, using a compartmental model of a pyramidal neuron, suggest that each of these two mechanisms could account for the activity-dependent attenuation and failure of the action potentials in the dendrites during the train. Each mechanism is shown to be in good qualitative agreement with experimental findings on somatic or dendritic stimulation and on the effects of hyperpolarization. The conditions under which branch point failures can be observed, and a few experimentally testable predictions, are presented and discussed. PMID:8913580

Legal action against health claims on foods and beverages marketed to youth.

PubMed

Rutkow, Lainie; Vernick, Jon S; Edwards, Danielle M; Rodman, Sarah O; Barry, Colleen L

2015-03-01

The prevalence of obesity among US children raises numerous health concerns. One pathway to reduce childhood obesity is by decreasing energy intake through the ingestion of fewer calories. Yet, food and beverage manufacturers often promote energy-dense items for children via varied health claims. Deceptive health claims are prohibited, and may be addressed through litigation or governmental regulatory efforts. While the amount of legal action against these potentially deceptive claims has increased, no comprehensive assessment has been conducted. This article, which analyzes litigation and governmental regulatory activities, considers key factors that may influence decisions to take legal action against potentially deceptive health claims on foods and beverages, including scientific support, forum selection, selection of plaintiffs, and potential public health impact.

Legal Action Against Health Claims on Foods and Beverages Marketed to Youth

PubMed Central

Vernick, Jon S.; Edwards, Danielle M.; Rodman, Sarah O.; Barry, Colleen L.

2015-01-01

The prevalence of obesity among US children raises numerous health concerns. One pathway to reduce childhood obesity is by decreasing energy intake through the ingestion of fewer calories. Yet, food and beverage manufacturers often promote energy-dense items for children via varied health claims. Deceptive health claims are prohibited, and may be addressed through litigation or governmental regulatory efforts. While the amount of legal action against these potentially deceptive claims has increased, no comprehensive assessment has been conducted. This article, which analyzes litigation and governmental regulatory activities, considers key factors that may influence decisions to take legal action against potentially deceptive health claims on foods and beverages, including scientific support, forum selection, selection of plaintiffs, and potential public health impact. PMID:25602904

Impaired action potential initiation in GABAergic interneurons causes hyperexcitable networks in an epileptic mouse model carrying a human Na(V)1.1 mutation.

PubMed

Hedrich, Ulrike B S; Liautard, Camille; Kirschenbaum, Daniel; Pofahl, Martin; Lavigne, Jennifer; Liu, Yuanyuan; Theiss, Stephan; Slotta, Johannes; Escayg, Andrew; Dihné, Marcel; Beck, Heinz; Mantegazza, Massimo; Lerche, Holger

2014-11-05

Mutations in SCN1A and other ion channel genes can cause different epileptic phenotypes, but the precise mechanisms underlying the development of hyperexcitable networks are largely unknown. Here, we present a multisystem analysis of an SCN1A mouse model carrying the NaV1.1-R1648H mutation, which causes febrile seizures and epilepsy in humans. We found a ubiquitous hypoexcitability of interneurons in thalamus, cortex, and hippocampus, without detectable changes in excitatory neurons. Interestingly, somatic Na(+) channels in interneurons and persistent Na(+) currents were not significantly changed. Instead, the key mechanism of interneuron dysfunction was a deficit of action potential initiation at the axon initial segment that was identified by analyzing action potential firing. This deficit increased with the duration of firing periods, suggesting that increased slow inactivation, as recorded for recombinant mutated channels, could play an important role. The deficit in interneuron firing caused reduced action potential-driven inhibition of excitatory neurons as revealed by less frequent spontaneous but not miniature IPSCs. Multiple approaches indicated increased spontaneous thalamocortical and hippocampal network activity in mutant mice, as follows: (1) more synchronous and higher-frequency firing was recorded in primary neuronal cultures plated on multielectrode arrays; (2) thalamocortical slices examined by field potential recordings revealed spontaneous activities and pathological high-frequency oscillations; and (3) multineuron Ca(2+) imaging in hippocampal slices showed increased spontaneous neuronal activity. Thus, an interneuron-specific generalized defect in action potential initiation causes multisystem disinhibition and network hyperexcitability, which can well explain the occurrence of seizures in the studied mouse model and in patients carrying this mutation. Copyright © 2014 the authors 0270-6474/14/3414874-16$15.00/0.

Excitability is increased in hippocampal CA1 pyramidal cells of Fmr1 knockout mice

PubMed Central

Luque, M. Angeles; Beltran-Matas, Pablo; Marin, M. Carmen; Torres, Blas

2017-01-01

Fragile X syndrome (FXS) is caused by a failure of neuronal cells to express the gene encoding the fragile mental retardation protein (FMRP). Clinical features of the syndrome include intellectual disability, learning impairment, hyperactivity, seizures and anxiety. Fmr1 knockout (KO) mice do not express FMRP and, as a result, reproduce some FXS behavioral abnormalities. While intrinsic and synaptic properties of excitatory cells in various part of the brain have been studied in Fmr1 KO mice, a thorough analysis of action potential characteristics and input-output function of CA1 pyramidal cells in this model is lacking. With a view to determining the effects of the absence of FMRP on cell excitability, we studied rheobase, action potential duration, firing frequency–current intensity relationship and action potential after-hyperpolarization (AHP) in CA1 pyramidal cells of the hippocampus of wild type (WT) and Fmr1 KO male mice. Brain slices were prepared from 8- to 12-week-old mice and the electrophysiological properties of cells recorded. Cells from both groups had similar resting membrane potentials. In the absence of FMRP expression, cells had a significantly higher input resistance, while voltage threshold and depolarization voltage were similar in WT and Fmr1 KO cell groups. No changes were observed in rheobase. The action potential duration was longer in the Fmr1 KO cell group, and the action potential firing frequency evoked by current steps of the same intensity was higher. Moreover, the gain (slope) of the relationship between firing frequency and injected current was 1.25-fold higher in the Fmr1 KO cell group. Finally, AHP amplitude was significantly reduced in the Fmr1 KO cell group. According to these data, FMRP absence increases excitability in hippocampal CA1 pyramidal cells. PMID:28931075

Azithromycin/chloroquine combination does not increase cardiac instability despite an increase in monophasic action potential duration in the anesthetized guinea pig.

PubMed

Fossa, Anthony A; Wisialowski, Todd; Duncan, J Neil; Deng, Shibing; Dunne, Michael

2007-11-01

Prolongation of the electrocardiogram QT interval by some, but not all drugs, has been associated with increased incidence of sudden cardiac death. Current preclinical regulatory assays cannot discriminate the arrhythmia liability of these drugs. Consequently, many new medications that prolong the QT interval are not developed despite their potential therapeutic benefit. Alternans (action potential duration alternations) is a measure of cardiac instability in humans and animals associated with the onset of ventricular fibrillation. Due to potential arrhythmia risk from observed QT prolongation, alternans was assessed in the anesthetized guinea pig after azithromycin or chloroquine alone and after combination treatment at clinically relevant concentrations proposed for the management of malaria. Chloroquine alone, but not azithromycin, caused a profound increase in action potential duration but with only minimal effects on alternans (approximately 10 ms). Azithromycin alone and in combination with chloroquine showed no increase in alternans beyond vehicle baseline responses indicating no additional arrhythmia liability.

Induction of temporally dissociated morphological and physiological differentiation of N1E-115 cells.

PubMed

Cosgrove, C; Cobbett, P

1991-07-01

Clonal cells derived from neural tumors have been widely used to study the processes of neuronal differentiation in vitro. The murine neuroblastoma clone N1E-115 has recently been shown to differentiate morphologically in response to removal of serum from the culture medium. In the present study, the nature and time course of electrophysiological differentiation of N1E-115 cells maintained in serum-free medium was examined. Differentiated cells had a higher resting potential and lower input conductance than nondifferentiated cells. Differentiated but not nondifferentiated cells generated current evoked action potentials, and differentiated cells fired spontaneous, repetitive action potentials after 13 days in serum-free medium. The rate of potential change during the depolarizing and repolarizing phases of the action potential became faster as the duration of maintenance of cells in serum-free medium increased. Remarkably, morphological differentiation appeared to be complete after exposure to serum-free medium for 5 days but electrophysiological differentiation was not complete until 13 days in this medium.

NeuroGrid: recording action potentials from the surface of the brain.

PubMed

Khodagholy, Dion; Gelinas, Jennifer N; Thesen, Thomas; Doyle, Werner; Devinsky, Orrin; Malliaras, George G; Buzsáki, György

2015-02-01

Recording from neural networks at the resolution of action potentials is critical for understanding how information is processed in the brain. Here, we address this challenge by developing an organic material-based, ultraconformable, biocompatible and scalable neural interface array (the 'NeuroGrid') that can record both local field potentials(LFPs) and action potentials from superficial cortical neurons without penetrating the brain surface. Spikes with features of interneurons and pyramidal cells were simultaneously acquired by multiple neighboring electrodes of the NeuroGrid, allowing for the isolation of putative single neurons in rats. Spiking activity demonstrated consistent phase modulation by ongoing brain oscillations and was stable in recordings exceeding 1 week's duration. We also recorded LFP-modulated spiking activity intraoperatively in patients undergoing epilepsy surgery. The NeuroGrid constitutes an effective method for large-scale, stable recording of neuronal spikes in concert with local population synaptic activity, enhancing comprehension of neural processes across spatiotemporal scales and potentially facilitating diagnosis and therapy for brain disorders.

Low K+-induced hyperpolarizations trigger transient depolarizations and action potentials in rabbit ventricular myocytes

PubMed Central

Akuzawa-Tateyama, M; Tateyama, M; Ochi, R

1998-01-01

The effects of large reductions of [K+]o on membrane potential were studied in isolated rabbit ventricular myocytes using the whole-cell patch clamp technique.Decreasing [K+]o from the normal level of 5.4 mm to 0.1 mm increased resting membrane potential (Vrest) from −75.6 ± 0.3 to −140.3 ± 1.9 mV (means ± s.e.m; n = 127), induced irregular, transient depolarizations with mean maximal amplitudes of 19.5 ± 1.5 mV and elicited action potentials in 56.7 % of trials. The action potentials exhibited overshoots of 37.9 ± 1.5 mV (n = 72) and sustained plateaux.Addition of 0.1 mm La3+ in the presence of 0.1 mm[K+]o significantly increased Vrest but decreased the amplitude of transient depolarizations and suppressed the firing of action potentials.Replacement of external Na+ or Cl− with N-methyl-D-glucamine or aspartate, respectively, or internal dialysis with 10 mm EGTA or BAPTA had little effect on low [K+]o-induced membrane potential changes.Hyperpolarizing voltage clamp pulses to potentials between −110 and −200 mV activated irregular inward currents that increased in amplitude and frequency with increasing hyperpolarization and were depressed by 0.1 mm La3+.The generation of transient depolarizations by low [K+]o can be explained as being a consequence of decreasing the inward rectifier K+ current (IK1) and the appearance of inward currents reflecting electroporation resulting from strong electric fields across the membrane. PMID:9824717

Low doses of alcohol potentiate GABA sub B inhibition of spontaneous activity of hippocampal CA1 neurons in vivo

DOE Office of Scientific and Technical Information (OSTI.GOV)

Criado, J.R.; Thies, R.

1991-03-11

Low doses of alcohol facilitate firing of hippocampal neurons. Such doses also enhance the inhibitory actions of GABA. Alcohol is known to potentiate inhibition via GABA{sub A} receptors. However, the effects of alcohol on GABA{sub B} receptor function are not understood. Spontaneous activity of single units was recorded from CA1 neurons of male rats anesthetized with 1.0% halothane. Electrical recordings and local application of drugs were done with multi-barrel pipettes. CA1 pyramidal neurons fired spontaneous bursts of action potentials. Acute alcohol decreased the interval between bursts, a mild excitatory action. Alcohol also more than doubled the period of complete inhibitionmore » produced by local application of both GABA and baclofen. These data suggest that GABA{sub B}-mediated inhibition is also potentiated by low doses of alcohol.« less

Alternans promotion in cardiac electrophysiology models by delay differential equations.

PubMed

Gomes, Johnny M; Dos Santos, Rodrigo Weber; Cherry, Elizabeth M

2017-09-01

Cardiac electrical alternans is a state of alternation between long and short action potentials and is frequently associated with harmful cardiac conditions. Different dynamic mechanisms can give rise to alternans; however, many cardiac models based on ordinary differential equations are not able to reproduce this phenomenon. A previous study showed that alternans can be induced by the introduction of delay differential equations (DDEs) in the formulations of the ion channel gating variables of a canine myocyte model. The present work demonstrates that this technique is not model-specific by successfully promoting alternans using DDEs for five cardiac electrophysiology models that describe different types of myocytes, with varying degrees of complexity. By analyzing results across the different models, we observe two potential requirements for alternans promotion via DDEs for ionic gates: (i) the gate must have a significant influence on the action potential duration and (ii) a delay must significantly impair the gate's recovery between consecutive action potentials.

Visual-motor recalibration in geographical slant perception

NASA Technical Reports Server (NTRS)

Bhalla, M.; Proffitt, D. R.; Kaiser, M. K. (Principal Investigator)

1999-01-01

In 4 experiments, it was shown that hills appear steeper to people who are encumbered by wearing a heavy backpack (Experiment 1), are fatigued (Experiment 2), are of low physical fitness (Experiment 3), or are elderly and/or in declining health (Experiment 4). Visually guided actions are unaffected by these manipulations of physiological potential. Although dissociable, the awareness and action systems were also shown to be interconnected. Recalibration of the transformation relating awareness and actions was found to occur over long-term changes in physiological potential (fitness level, age, and health) but not with transitory changes (fatigue and load). Findings are discussed in terms of a time-dependent coordination between the separate systems that control explicit visual awareness and visually guided action.

Neural correlates of action perception at the onset of functional grasping

PubMed Central

Daum, Moritz M.; Handl, Andrea; Gredebäck, Gustaf

2015-01-01

Event-related potentials were recorded while infants observe congruent or incongruent grasping actions at the age when organized grasping first emerges (4–6 months of age). We demonstrate that the event-related potential component P400 encodes the congruency of power grasps at the age of 6 months (Experiment 1) and in 5-month-old infants that have developed the ability to use power grasps (Experiment 2). This effect does not extend to precision grasps, which infants cannot perform (Experiment 3). Our findings suggest that infants’ encoding of the relationship between an object and a grasping hand (the action–perception link) is highly specialized to actions and manual configurations of actions that infants are able to perform. PMID:25193947

Faculty Planning and Affirmative Action

ERIC Educational Resources Information Center

Linnell, Robert H.; Gray, Paul

1977-01-01

The use of a model to examine the impact of affirmative action policies on the female/male ratio of a faculty of natural sciences is reported. Increased analysis and detailed study of suggested alternatives can lead to better resolution of the problems and potentials of affirmative action programs. (LBH)

The Timing and Construction of Preference: A Quantitative Study

ERIC Educational Resources Information Center

Kendrick, Kobin H.; Torreira, Francisco

2015-01-01

Conversation-analytic research has argued that the timing and construction of preferred responding actions (e.g., acceptances) differ from that of dispreferred responding actions (e.g., rejections), potentially enabling early response prediction by recipients. We examined 195 preferred and dispreferred responding actions in telephone corpora and…

Visual context modulates potentiation of grasp types during semantic object categorization.

PubMed

Kalénine, Solène; Shapiro, Allison D; Flumini, Andrea; Borghi, Anna M; Buxbaum, Laurel J

2014-06-01

Substantial evidence suggests that conceptual processing of manipulable objects is associated with potentiation of action. Such data have been viewed as evidence that objects are recognized via access to action features. Many objects, however, are associated with multiple actions. For example, a kitchen timer may be clenched with a power grip to move it but pinched with a precision grip to use it. The present study tested the hypothesis that action evocation during conceptual object processing is responsive to the visual scene in which objects are presented. Twenty-five healthy adults were asked to categorize object pictures presented in different naturalistic visual contexts that evoke either move- or use-related actions. Categorization judgments (natural vs. artifact) were performed by executing a move- or use-related action (clench vs. pinch) on a response device, and response times were assessed as a function of contextual congruence. Although the actions performed were irrelevant to the categorization judgment, responses were significantly faster when actions were compatible with the visual context. This compatibility effect was largely driven by faster pinch responses when objects were presented in use-compatible, as compared with move-compatible, contexts. The present study is the first to highlight the influence of visual scene on stimulus-response compatibility effects during semantic object processing. These data support the hypothesis that action evocation during conceptual object processing is biased toward context-relevant actions.

Visual context modulates potentiation of grasp types during semantic object categorization

PubMed Central

Kalénine, Solène; Shapiro, Allison D.; Flumini, Andrea; Borghi, Anna M.; Buxbaum, Laurel J.

2013-01-01

Substantial evidence suggests that conceptual processing of manipulable objects is associated with potentiation of action. Such data have been viewed as evidence that objects are recognized via access to action features. Many objects, however, are associated with multiple actions. For example, a kitchen timer may be clenched with a power grip to move it, but pinched with a precision grip to use it. The present study tested the hypothesis that action evocation during conceptual object processing is responsive to the visual scene in which objects are presented. Twenty-five healthy adults were asked to categorize object pictures presented in different naturalistic visual contexts that evoke either move- or use-related actions. Categorization judgments (natural vs. artifact) were performed by executing a move- or use-related action (clench vs. pinch) on a response device, and response times were assessed as a function of contextual congruence. Although the actions performed were irrelevant to the categorization judgment, responses were significantly faster when actions were compatible with the visual context. This compatibility effect was largely driven by faster pinch responses when objects were presented in use- compared to move-compatible contexts. The present study is the first to highlight the influence of visual scene on stimulus-response compatibility effects during semantic object processing. These data support the hypothesis that action evocation during conceptual object processing is biased toward context-relevant actions. PMID:24186270