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an enhanced activity of L-type calcium channels at membrane potentials negative to 50 mV. This behaviorSomatic Colocalization of Rat SK1 and D class (Cav 1.2) L-type Calcium Channels in Rat CA1-activated potassium (SK) channels by calcium (Ca2 ) entry through L-type Ca2 channels. However, the ...

L-type Ca²⁺ channel C terminus calmodulin (CaM)-binding domains are molecular determinants for Ca²⁺�CaM-dependent increases in L-type Ca²⁺ current (I_Ca), and a ...

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The activity of single L-type Ca-+ channels was recorded from cell-attached patches on acutely isolated skeletal muscle fibers from the mouse. The experiments were concerned with the mechanism by which aminoglycoside antibiotics inhibit ion flow through t...

We previously demonstrated electrophysiologically that 1,25-dihydroxyvitamin D3 [1,25(OH)2D3] shifts

There is growing evidence for the role of voltage-gated L-type Ca²⁺ channels in mediating aspects of the addictive properties of psychostimulants. L-type Ca²⁺ channels activate Ca²⁺ second-messenger pathways that regulate ...

The goal of this study was to examine the relationship between Ca2+ entry through L-type Ca2+ channels and local [Ca2+]i transients (Ca2+ sparks) in single rat cardiac ventricular cells. L-type Ca2+ channels were activated by depolarization of ...

Ca(v)1.3 (alpha 1D) L-type Ca(2+) channels have been implicated in substantia nigra (SN) dopamine (DA) neuron pacemaking and vulnerability to Parkinson's disease. These effects may arise from the depolarizing current and cytoplasmic Ca(2+) elevation produced by Ca(v)1.3 channels at subthreshold ...

Exocytosis of extrusomes, secretory granules found in protozoa, is involved in prey capture by the heliozoon Actinophrys sol. Here, we show that extracellular Ca(2+) is necessary for exocytosis and prey capture in A. sol. We found that A. sol could not capture prey cells in a Ca(2+)-free solution. L-type Ca(2+) ...

Subcellularly localized Ca2+ signals in cardiac and skeletal muscle have recently been identified as elementary Ca2+ signaling events. The signals, termed Ca2+ sparks and Ca2+ quarks, represent openings of Ca2+ release channels located in the membrane of the sarcoplasmic reticulum (SR). In ...

It has been suggested that protein tyrosine kinase (PTK) activity can directly regulate cardiac L-type Ca(2+) channels. This conclusion is based to a large extent on the observation that the PTK inhibitor genistein can inhibit the cardiac L-type Ca(2+) current. The purpose of the present study was to determine ...

BACKGROUND: In heart failure, the Na+-Ca�+ exchanger (NCX) is upregulated and mediates Ca�+ influx (instead of efflux) during the cardiac action potential. Although this partly compensates for impaired sarcoplasmic reticulum Ca�+ release and supports inotropy, the energetic consequences have never been considered. Because ...

with the nonselective protein phosphatase inhibitors microcystin or okadaic acid pro- duced an increase in the L-type Ca current (/ca) and a decrease in the delayed rec- tifier K current (IK). We hypothesized that microcystin the nature of PKX and its phosphorylation tar- get. The effect of internal perfusion with microcystin on /Ca

At most synapses, presynaptic Ca(2+) channels are positioned near vesicle release sites, and increasing this distance reduces synaptic strength. We examined the lateral membrane mobility of presynaptic L-type Ca(2+) channels at photoreceptor ribbon synapses of the tiger salamander (Ambystoma tigrinum) retina. Movements of individual ...

To investigate the cellular mechanisms for altered Ca2+ homeostasis and contractility in cardiac hypertrophy, we measured whole-cell L-type Ca2+ currents (ICa,L), whole-cell Ca2+ transients ([Ca2+]i), and Ca2+ sparks in ventricular cells from 6-month-old spontaneously ...

Dopaminergic neurons of the substantia nigra pars compacta are autonomous pacemakers. This activity is responsible for the sustained release of dopamine necessary for the proper functioning of target structures like the striatum. Somatodendritic L-type Ca²⁺ channels have long been viewed as important, if not necessary, for this ...

Atrioventricular node (AV node) is the hub where electrical input from the atria is propagated and conveyed to the ventricles. Despite its strategic position and role in governing impulse conduction between atria and ventricles, there is paucity of data regarding the contribution of specific ion channels to the function of the AV node. Here, we examined the roles of Ca(v)1.3 ...

1. Single-channel studies were performed to clarify how tonic changes in intracellular Ca2+ concentrations ([Ca2+]i) modulate cardiac L-type Ca2+ channels. Currents were recorded from fura-2-loaded guinea-pig ventricular myocytes in the cell-attached configuration. Fura-2 fluorescence signals were recorded ...

Myocardial cells have two types of Ca channels commonly called T-type and L-type. Whole cell Ca channel currents in guinea pig atrial myocytes can be separated and quantitated by analyzing channel closing kinetics after a brief depolarization (tail current analysis). L-type Ca channels deactivate rapidly when the ...

Glutamate-induced rise in the intracellular Ca²⁺ level is thought to be a major cause of excitotoxic cell death, but the mechanisms that control the Ca²⁺ overload are poorly understood. Using immunocytochemistry, electrophysiology and Ca²⁺ imaging, we show that ...

Presynaptic inhibition is a major mechanism for regulating synaptic transmission in the CNS and adenosine inhibits Ca(2+) currents (I(Ca)) to reduce transmitter release at several synapses. Rod photoreceptors possess L-type Ca(2+) channels that regulate the release of L-glutamate. In the retina, adenosine is ...

Voltage-dependent Ca channels are classified into several subtypes based on the isoform of their ?1 subunits. Traditional Ca channels blockers (CCBs), including nifedipine and amlodipine, act predominantly on L-type Ca channels, whereas novel CCBs such as efonidipine, benidipine and azelnidipine inhibit both L-type ...

SummaryNeuronal L-type calcium channels contribute to dendritic excitability and activity-dependent changes in gene expression that influence synaptic strength. Phosphorylation-mediated enhancement of L-type channels containing the Ca_V1.2 pore-forming subunit is promoted by A-kinase anchoring proteins (AKAPs) that target ...

used in these analy- ses, imaging of fluorescent membrane impermeable E2- BSA-FITC was performed (Fig -estradiol; E2-BSA-FITC, 17 -estradiol�bovine serum albumin�fluorescein isothiocyanate macromolecular complex by the Institutional Animal Care and Use Committee at the University of Southern California (Los An- geles, CA, USA

L-type Ca(2+) channels in mammalian brain neurons have either a Ca(V)1.2 or Ca(V)1.3 pore-forming subunit. Recently, it was shown that Ca(V)1.3 Ca(2+) channels underlie autonomous pacemaking in adult dopaminergic neurons in the substantia nigra pars compacta, and this ...

A unique transient outward K(+) current (I(to)) has been described to result from the removal of extracellular Ca(2+) from ventricular myocytes of the guinea pig (15). This study addressed the question of whether this current represented K(+)-selective I(to) or the efflux of K(+) via L-type Ca(2+) channels. This outward current was ...

Ca_V1.3 L-type channels control inner hair cell (IHC) sensory and sinoatrial node (SAN) function, and excitability in central neurons by means of their low-voltage activation and inactivation properties. In SAN cells Ca_V1.3 inward calcium current ...

Some studies report that the positive relationship between L-type Ca²⁺ current (I_Ca?L) and frequency in cardiac myocytes is mainly due to a direct negative feedback of sarcoplasmic reticulum Ca²⁺ release on ...

1. Subcellularly localized Ca2+ signals have been proposed to represent elementary events of cardiac Ca2+ signalling (Ca2+ sparks), whereby an individual sarcolemmal L-type Ca2+ channel locally controls opening of a single (or a few) Ca2+ release channels in the ...

1. Subcellularly localized Ca2+ signals have been proposed to represent elementary events of cardiac Ca2+ signalling (Ca2+ sparks), whereby an individual sarcolemmal L-type Ca2+ channel locally controls opening of a single (or a few) Ca2+ release channels in the ...

Ca_v1 (L-type) channels and calmodulin-dependent protein kinase II (CaMKII) are key regulators of Ca²⁺ signaling in neurons. CaMKII directly potentiates the activity of Ca_v1.2 and ...

The Ca²⁺/calmodulin-dependent protein phosphatase, calcineurin, modulates a number of key Ca²⁺ signaling pathways in neurons, and has been implicated in Ca²⁺-dependent negative feedback inactivation of N-methyl-d-aspartate receptors and voltage-sensitive ...

The inactivation of voltage-gated L-type Ca(2+) channels (Ca(V)1) regulates Ca(2+) entry and controls intracellular Ca(2+) levels that are essential for cellular activity. The molecular entities implicated in L-channel (Ca(V)1.2) inactivation are not fully identified. Here ...

Ca2+ signals in cardiac muscle cells are composed of spatially limited elementary events termed Ca2+ sparks. Several studies have also indicated that Ca2+ signals smaller than Ca2+ sparks can be elicited. These signals have been termed Ca2+ quarks and were proposed to result from the opening of ...

CaV1.3 L-type channels control inner hair cell (IHC) sensory and sinoatrial node (SAN) function, and excitability in central neurons by means of their low-voltage activation and inactivation properties. In SAN cells CaV1.3 inward calcium current (ICa) inactivates rapidly whereas in IHCs inactivation is slow. A candidate suggested in ...

1. We investigated the currents through L-type Ca2+ channels when Ca2+ (1-10 mM) was the charge carrier, as is the case physiologically. 2. Na+ was removed from both the external and internal solutions to eliminate currents through Na+ channels and Na(+)-Ca2+ exchange. 3. From a holding potential of -50 mV only ...

Ca + Ileak - Iup + Irel (34) are affected by the L-type calcium current ICaL, the background calcium current conductance Cmax CaL = 0.175mm3 �F-1 s-1 , the maxi- mum background calcium conductance Cmax bCa = 0.000592n the plateau, the net influx of positively charged calcium ions through L-type sodium channels is ...

Ca + Ileak - Iup + Irel (34) are affected by the L-type calcium current ICaL, the background calcium current conductance Cmax CaL = 0.175mm3 �F-1 s-1 , the maxi- mum background calcium conductance Cmax bCa = 0.000592n charged calcium ions through L-type sodium channels is balanced by the efflux of positively ...

Ca(2+) mediates the functional coupling between L-type Ca(2+) channel (LTCC) and sarcoplasmic reticulum (SR) Ca(2+) release channel (ryanodine receptor, RyR), participating in key pathophysiological processes. This crosstalk manifests as the orthograde Ca(2+)-induced ...

Voltage-gated Ca2+ channels in vertebrates comprise at least seven molecular subtypes, each of which produces a current with distinct kinetics and pharmacology. Although several invertebrate Ca2+ channel alpha1 subunits have also been cloned, their functional characteristics remain unclear, as heterologous expression of a full-length invertebrate channel ...

The venoms of Latrodectus sp. have been reported to induce contraction probably mediated by adrenergic and cholinergic transmitters. We have demonstrated that the venom of Chilean Latrodectus mactans contains neurotoxins that induce a contraction partially independent of transmitters release. Transmembrane mobility of Na+ and Ca2+ ions and more specifically, the increase of ...

Myopathies in critically ill patients are increasingly documented. Various animal models of chronic sepsis have been employed to investigate reduced membrane excitability or altered isometric contractility of skeletal muscle. In contrast, immediate changes occurring during acute sepsis are significantly under-characterised; L-type Ca(2+) channel function ...

In smooth muscle of the guinea-pig bladder, either membrane potential recordings or [Ca²⁺]_i measurements were made simultaneously with isometric tension recordings.Single transmural stimuli initiated excitatory junction potentials (EJPs) which triggered action potentials, transient increases in ...

The changes in cytosolic Ca2+ levels play important roles in the signal transduction pathways of many environmental and developmental stimuli in plants and animals. We demonstrated that the increase in cytosolic free Ca2+ concentration ([Ca2+]cyt) of Arabidopsis thaliana leaf cells was induced by exogenous application of jasmonic acid ...

Heavy metals, including gold, induce severe contact hypersensitivity and autoimmune disorders, which develop through an initial Th2-independent process followed by a Th2-dependent process. It has been shown that mast cell activation plays a role in the Th2-independent process and that gold stimulates histamine release in vitro. However, the mechanisms of the gold-induced mast cell activation ...

The insulin IGF-1�PI3K�Akt signaling pathway has been suggested to improve cardiac inotropism and increase Ca²⁺ handling through the effects of the protein kinase Akt. However, the underlying molecular mechanisms remain largely unknown. In this study, we provide evidence for an unanticipated regulatory function of Akt controlling ...

We have investigated the modifications of cytosolic [Ca2+] and the activity of Ca2+ channels in freshly dispersed arterial myocytes to test whether lowering O_2 tension (PO_2) directly influences Ca2+ homeostasis in these cells. Unclamped cells loaded with fura-2 AM exhibit oscillations of cytosolic Ca2+ whose ...

The engagement of integrin ?7 in E63 skeletal muscle cells by laminin or anti-?7 antibodies triggered transient elevations in the intracellular free Ca²⁺ concentration that resulted from both inositol triphosphate-evoked Ca²⁺ release from intracellular stores and extracellular ...

Voltage-dependent Ca(2+) channels have been divided into at least 5 types (L-, N-, T-, P-, and Q-type). L/N-type Ca(2+) channel blocker cilnidipine could reduce the size of cerebral infarction in the rat focal brain ischemia. L-type Ca(2+) channel blocker amlodipine reduced cerebral edema and inhibit neuronal cell ...

FIGURE 1. Proteins involved in calcium signaling in mammalian ventricular myocytes. Junctional sarcoplasmic reticulum (SR) membrane in close proximity to the sarcolemma forms dyads, which are present mainly in the transverse tubules (TT) but also at the surface membrane. Dyads comprise a cluster of ryanodine receptors (RyRs) adjacent to, and under the functional control of, ...

L-type Ca channels play a fundamental role in cardiomyocyte excitation and contraction and are functionally regulated by transient activation of ?-adrenergic receptors. However, long-term ?-adrenergic signaling has been implicated in the development of pathophysiological conditions including cardiac hypertrophy. Regulation of L-type channels may be ...

Ca(v)1.3 (L-type) voltage-gated Ca2+ channels have emerged as key players controlling Ca2+ signals at excitatory synapses. Compared with the more widely expressed Ca(v)1.2 L-type channel, relatively little is known about the mechanisms that regulate ...

An undefined property of L-type Ca2+ channels is believed to underlie the unique phenotype of hibernating hearts. Therefore, L-type Ca2+ channels in single cardiomyocytes isolated from hibernating versus awake ground-squirrels (Citellus undulatus) were compared using the perforated mode of the patch-clamp technique, and interpreted by ...

Rationale: L-type Ca(2+) (Ca(V)1.2) channels shape the cardiac action potential waveform and are essential for excitation-contraction coupling in heart. A gain-of-function G406R mutation in a cytoplasmic loop of Ca(V)1.2 channels causes long QT syndrome 8 (LQT8), a disease also known as Timothy syndrome. However, ...

Oestrogen can modify the contractile function of vascular smooth muscle and cardiomyocytes. The negative inotropic actions of oestrogen on the heart and coronary vasculature appear to be mediated by L-type Ca{sup 2+} channel (Ca{sub v}1.2) inhibition, but the underlying mechanisms remain elusive. We tested the hypothesis that oestrogen directly inhibits ...

Cellular Ca²⁺ signaling underlies diverse vital biological processes, including muscle contractility, memory encoding, fertilization, cell survival, and cell death. Despite extensive studies, the fundamental control mechanisms that regulate intracellular Ca²⁺ movement remain enigmatic. We have found ...

Voltage-gated Ca²⁺ channels couple membrane depolarization to Ca²⁺-dependent intracellular signaling events. This is achieved by mediating Ca²⁺ ion influx or by direct conformational coupling to intracellular Ca²⁺ release ...

During activation of the sympathetic nervous system, cardiac performance is increased as part of the fight-or-flight stress response. The increase in contractility with sympathetic stimulation is an orchestrated combination of intrinsic inotropic, lusitropic, and chronotropic effects, mediated in part by activation of beta-adrenergic receptors and protein kinase A. This causes phosphorylation of ...

During activation of the sympathetic nervous system, cardiac performance is increased as part of the fight-or-flight stress response. The increase in contractility with sympathetic stimulation is an orchestrated combination of intrinsic inotropic, lusitropic and chronotropic effects, mediated in part by activation of ?-adrenergic receptors and protein kinase A. This causes phosphorylation of ...

MYD11A1-D, day 2003198 (07/17/2003), Science Test C6.5.2-New. previous � next � View: C6.5.2-Baseline Product: MYD11A1-D Date: 2003198 Pixel size: 40km, ...

MOD11A1-D, day 2003197 (07/16/2003), Science Test C6.5.2-New. previous � next � View: C6.5.2-Baseline Product: MOD11A1-D Date: 2003197 Pixel size: 40km, ...

MOD11A1-D, day 2008004 (01/4/2008), Science Test C6.5-New. previous � next � View: C6.5-Baseline Product: MOD11A1-D Date: 2008004 Pixel size: 40km, C65-LST ...

Mibefradil is a novel Ca²⁺ antagonist which blocks both high-voltage activated and low voltage-activated Ca²⁺ channels. Although L-type Ca²⁺ channel block was demonstrated in functional experiments its molecular interaction with the channel has ...

In skeletal muscle, there is bidirectional signalling between the L-type Ca(2+) channel (1,4-dihydropyridine receptor; DHPR) and the type 1 ryanodine-sensitive Ca(2+) release channel (RyR1) of the sarcoplasmic reticulum (SR). In the case of "orthograde signalling" (i.e., excitation-contraction coupling), the conformation of RyR1 is controlled by ...

The application of confocal microscopy to cardiac and skeletal muscle has resulted in the observation of transient, spatially localized elevations in [Ca2+]i, termed 'Ca2+ sparks'. Ca2+ sparks are thought to represent 'elementary' Ca2+ release events, which arise from one or more ryanodine receptor (RyR) channels ...

Calmodulin (CaM) binding to the intracellular C-terminal tail (CTT) of the cardiac L-type Ca(2+) channel (Ca(V)1.2) regulates Ca(2+) entry by recognizing sites that contribute to negative feedback mechanisms for channel closing. CaM associates with ...

This review compares ryanodine receptor (RyR)-mediated Ca(2+) signaling processes in muscle and osteoclast cells. In muscle, RyR-mediated release of an intracellularly stored, sarcoplasmic reticular (SR), Ca(2+) is triggered by voltage-sensitive dihydropyridine receptor (DHPR)-L-type Ca(2+) channels either through ...

In arterial vascular smooth muscle cells (VSMCs), Ca²⁺ sparks stimulate nearby Ca²⁺-activated K⁺ (BK) channels that hyperpolarize the membrane and close L-type Ca²⁺ channels. We tested the contribution of L-type ...

Patch-clamp and fluorescence measurements of cytoplasmic Ca(2+) concentration ([Ca(2+)](i)) were performed to directly detect extracellular Ca(2+) entry into cultured parathyroid cells from patients with secondary hyperparathyroidism. Cells loaded with fluo-3 AM or fluo-4 AM showed a transient increase in fluorescence ...

Voltage-dependent calcium channels (Ca(V)) open in response to changes in membrane potential, but their activity is modulated by Ca(2+) binding to calmodulin (CaM). Structural studies of this family of channels have focused on CaM bound to the IQ motif; however, the minimal differences between structures cannot ...

Intracellular Ca(2+) regulates numerous proteins and cellular functions and can vary substantially over submicron and submillisecond scales, so precisely localized fast detection is desirable. We have created a approximately 1-kDa biarsenical Ca(2+) indicator, called Calcium Green FlAsH (CaGF, 1), to probe [Ca(2+)] ...

Intracellular Ca²⁺ regulates numerous proteins and cellular functions and can vary substantially over submicron and submillisecond scales, so precisely localized fast detection is desirable. We have created a ~1-kDa biarsenical Ca²⁺ indicator, called Calcium Green FlAsH (CaGF, 1), to probe ...

Vertebrate photoreceptors consist of strictly delimited subcellular domains: the outer segment, ellipsoid, cell body and synaptic terminal, each hosting crucial cellular functions, including phototransduction, oxidative metabolism, gene expression and transmitter release. We used optical imaging to explore the spatiotemporal dynamics of Ca(2+) signaling in non-outer segment ...

Vertebrate photoreceptors consist of strictly delimited subcellular domains: the outer segment, ellipsoid, cell body and synaptic terminal, each hosting crucial cellular functions, including phototransduction, oxidative metabolism, gene expression and transmitter release. We used optical imaging to explore the spatiotemporal dynamics of Ca²⁺ signaling in ...

Ca(2+) entry through L-type calcium channels (Ca(V)1.2) is critical in shaping the cardiac action potential and initiating cardiac contraction. Modulation of Ca(V)1.2 channel gating directly affects myocyte excitability and cardiac function. We have found that phospholemman (PLM), a member of the FXYD family and ...

AbstractCa²⁺ entry through L-type calcium channels (Ca_V1.2) is critical in shaping the cardiac action potential and initiating cardiac contraction. Modulation of Ca_V1.2 channel gating directly affects myocyte excitability and cardiac function. We ...

1. The extracellular glutamate content and Ca2+ level in vivo in rat hippocampus were measured by brain microdialysis following administration of two depolarizing agents (veratridine, KCl) and quinolinic acid (Quin). 2. The two depolarizing agents increased the extracellular glutamate level (to between 280 and 320% basal) and decreased the extracellular ...

1. The extracellular glutamate content and Ca2+ level in vivo in rat hippocampus were measured by brain microdialysis following administration of two depolarizing agents (veratridine, KCl) and quinolinic acid (Quin). 2. The two depolarizing agents increased the extracellular glutamate level (to between 280 and 320% basal) and decreased the extracellular ...

L-type calcium currents conducted by CaV1.2 channels initiate excitation-contraction coupling in cardiac and vascular smooth muscle. In the heart, the distal portion of the C terminus (DCT) is proteolytically processed in vivo and serves as a noncovalently associated autoinhibitor of CaV1.2 channel activity. This autoinhibitory ...

light�dark cycle and regulates circadian rhythms. The SCN is composed of multiple neurons with cell; Circadian rhythm; Nifedipine; 4-Aminopyridine; L-type Ca2+ current; Fast delayed rectifier K+ current a circadian rhythm of firing rate that lasts for many days (Welsh et al., 1995; Herzog et al., 1998; Honma et

of the niphedipine, verapamil and bafilomycin experiments using the ion-specific microelectrodes, all experiments blocker, was applied as was verapamil, another voltage-dependent L-type Ca2+ channel blocker and 1 Louis, MO, USA), 10moll�1 verapamil hydrochloride (Sigma-Aldrich), 10moll�1 La3+ or 100moll�1 La3+ as La

Glucagon-like peptide-2 (GLP-2) is a neuropeptide secreted from endocrine cells in the gut and neurons in the brain. GLP-2 stimulates intestinal crypt cell proliferation and mucosal blood flow while decreasing gastric emptying and gut motility. However, a GLP-2-mediated signaling network has not bee...

characteristics (de- creased response to verapamil and decreased resting poten- tial) were noted in microelectrode- tients, but not those with AF, was attenuated in response to verapamil. Boutjdir et al4 demonstrated, Van Gelder IC, de Kam PJ, Grandjean J, Bel KJ, Wijffels MC, Allessie MA, Crijns HJ. Verapamil reduces

Transient receptor potential vanilloid 1 (TRPV1) functions as a polymodal nociceptor and is activated by several vanilloids, including capsaicin, protons and heat. Although TRPV1 channels are widely distributed in the brain, their roles remain unclear. Here, we investigated the roles of TRPV1 in cytotoxic processes using TRPV1-expressing cultured rat cortical neurons. Capsaicin induced severe ...

Insulin release by pancreatic ?-cells is regulated by diverse intracellular signals, including changes in Ca(2+) concentration resulting from Ca(2+) entry through voltage-gated (Ca(V)) channels. It has been reported that the Rab3 effector RIM1 acts as a functional link between neuronal Ca(V) channels and the ...

Two processes dominate voltage-gated calcium channel (Ca_V) inactivation: voltage-dependent inactivation (VDI) and calcium-dependent inactivation (CDI). The Ca_V?/Ca_V?₁-I-II loop and Ca²⁺/calmodulin ...

Intracellular Ca2+ can inhibit the activity of voltage-gated Ca channels by modulating the rate of channel inactivation. Ca(2+)-dependent inactivation of these channels may be a common negative feedback process important for regulating Ca2+ entry under physiological and pathological conditions. This article ...

L-type (alpha(1C)) calcium channels inactivate rapidly in response to localized elevation of intracellular Ca(2+), providing negative Ca(2+) feedback in a diverse array of biological contexts. The dominant Ca(2+) sensor for such Ca(2+)-dependent inactivation has recently been identified as ...

The calcium ion plays a unique role as a messenger and a cofactor in cardiac contraction. This role relies on the strict control by the cell of Ca homeostasis, the components of which are described in this review. During the few last years, tools for the measurement of free intracellular Ca in living cells have been developed which include: probes ...

Communication between cell surface proteins and the nucleus is integral to many cellular adaptations. In the case of ion channels in excitable cells, the dynamics of signaling to the nucleus are particularly important because the natural stimulus, surface membrane depolarization, is rapidly pulsatile. To better understand excitation�transcription coupling we characterized the dependence of cAMP ...

The patch-clamp technique was employed to investigate the response of single L-type Ca2+ channels to the protease trypsin applied to the intracellular face of excised membrane patches from guinea pig ventricular myocytes. Calpastatin and ATP were used to prevent run-down of Ca2+ channel activity monitored with 96 mM Ba2+ as charge ...

The contraction of adult mammalian ventricular cardiomyocytes is triggered by the influx of Ca(2+) ions through sarcolemmal L-type Ca(2+) channels (LCCs). However, the gating properties of unitary LCCs under physiologic conditions have remained elusive. Towards this end, we investigated the voltage-dependence of the gating kinetics of ...

The present study was conducted to investigate the effects of the diabetic condition on cytosolic free Ca(2+) concentration, [Ca(2+)](i), and the proliferation of splenic lymphocytes from mice. Diabetes was induced in mice by intraperitoneal injection of alloxan. [Ca(2+)](i) and the proliferation ex vivo of splenic lymphocytes isolated ...

Calcium sparks represent local, rapid, and transient calcium release events from a cluster of ryanodine receptors (RyRs) in the sarcoplasmic reticulum. In arterial smooth muscle cells (SMCs), calcium sparks activate calcium-dependent potassium channels causing decrease in the global intracellular [Ca²⁺] and oppose vasoconstriction. This is in contrast to ...

Complex modulation of voltage-gated Ca2+ currents through the interplay among Ca2+ channels and various Ca(2+)-binding proteins is increasingly being recognized. The K+ channel interacting protein 2 (KChIP2), originally identified as an auxiliary subunit for K(V)4.2 and a component of the transient outward K+ channel (I(to)), is a ...

In arterial smooth muscle, protein kinase C? (PKC?) coerces discrete clusters of L-type Ca²⁺ channels to operate in a high open probability mode, resulting in subcellular domains of nearly continual Ca²⁺ influx called �persistent Ca²⁺ sparklets�. Our previous work ...

In cardiac ventricular myocytes, calcium (Ca) release occurs at distinct structures (dyads) along t-tubules, where L-type Ca channels (LCCs) appose sarcoplasmic reticulum (SR) Ca release channels (RyR2s). We developed a model of the cardiac ventricular myocyte that simulates local stochastic Ca ...

Recently, it has become possible to record the localized fluorescence transient associated with the opening of a single plasma membrane Ca(2+) permeable ion channel using Ca(2+) indicators like fluo-3. These Single Channel Ca(2+) Fluorescence Transients (SCCaFTs) share some of the characteristics of such elementary events as ...

The green tea polyphenol (-)-epigallocatechin-3-O-gallate (EGCG) has various biological activities, including anti-inflammatory, anti-neoplastic, anti- and pro-apoptotic, and neuroprotective effects. Although these are often associated with increased intracellular reactive oxygen species (ROS) and Ca(2+) levels, their involvement in biological effects is poorly understood. ...

The L-type Ca(2+) channel Ca(v)1.2 forms macromolecular signaling complexes that comprise the ?(2) adrenergic receptor, trimeric G(s) protein, adenylyl cyclase, and cAMP-dependent protein kinase (PKA) for efficient signaling in heart and brain. The protein phosphatases PP2A and PP2B are part of this complex. PP2A counteracts increase in ...

At most synapses, presynaptic Ca²⁺ channels are positioned near vesicle release sites, and increasing this distance reduces synaptic strength. We examined the lateral membrane mobility of presynaptic L-type Ca²⁺ channels at photoreceptor ribbon synapses of the tiger salamander (Ambystoma ...

Excitation-induced Ca(2+) cycling into and out of the cytosol via the sarcoplasmic reticulum (SR) Ca(2+) pump, ryanodine receptor (RyR) and Na(+)-Ca(2+) exchanger (NCX) proteins, and modulation of this Ca(2+)cycling by beta-adrenergic receptor (beta-AR) stimulation, governs the strength of ventricular myocyte ...

By now, little is known on L-type calcium channel (LTCC) subunits expressed in mouse heart. We show that CaV?2 proteins are the major CaV? components of the LTCC in embryonic and adult mouse heart, but that in embryonic heart CaV?3 proteins are also detectable. At least two CaV?2 variants of ?68 and ?72 kDa are ...

In neurons L-type calcium currents function in gene regulation and synaptic plasticity, while excessive calcium influx leads to excitotoxicity and neurodegeneration. The major neuronal Ca(V)1.2 L-type channels are localized in clusters in dendritic shafts and spines. Whereas Ca(V)1.2 clusters remain stable during ...

Ca²⁺ sparks are the elementary release events in many types of cells. Here we present a morphometric analysis of Ca²⁺ sparks (i.e., amplitude and kinetic parameters) using an approach that minimizes the confounding factor of the detection of out-of-focus events. By activation and visualization of ...

We previously reported that piceatannol isolated from the rhizome extract of RHEUM UNDULATUM has a potent vasorelaxant activity. In the present study, the mechanisms underlying the direct vascular relaxant effect of piceatannol were investigated in isolated rat aorta. Piceatannol induced a concentration-dependent relaxation in aortic preparations precontracted with phenylephrine (EC (50) : 2.4 +/- ...

Ca²⁺/calmodulin-dependent protein kinase II (CaMKII) plays an important role in L-type Ca²⁺ channel (LCC) facilitation: the Ca²⁺-dependent augmentation of Ca²⁺ current ...

Cardiac L-type voltage-dependent Ca(2+) channels are heteromultimeric polypeptide complexes of alpha(1)-, alpha(2)/delta-, and beta-subunits. The alpha(2)/delta-1-subunit possesses a stereoselective, high-affinity binding site for gabapentin, widely used to treat epilepsy and postherpetic neuralgic pain as well as sleep disorders. Mutations in ...

Recordings of single-channel activity from cerebellar granule cells show that a component of Ca2+ entry flows through L-type Ca2+ channels that are closed at negative membrane potentials following a strong depolarization, but then open after a delay. The delayed openings can be explained if membrane depolarization drives ...

Synapse formation is tightly associated with neuronal excitability. We found striking synaptic overgrowth caused by Drosophila K(+)-channel mutations of the seizure and slowpoke genes, encoding Erg and Ca(2+)-activated large-conductance (BK) channels, respectively. These mutants display two distinct patterns of "satellite" budding from larval motor terminus synaptic boutons. ...

Hypertension, atherosclerosis, and resultant chronic heart failure (HF) reach epidemic proportions among older persons, and the clinical manifestations and the prognoses of these worsen with increasing age. Thus, age per se is the major risk factor for cardiovascular disease. Changes in cardiac cell phenotype that occur with normal aging, as well as in HF associated with aging, include deficits in ...

Voltage patch-clamp experiments at the whole-vacuole and single-channel levels were employed to study the retrieval of Ca2+ from vacuoles into the cytoplasm in sugar beet cell (Beta vulgaris L.) suspension cultures. Channels allowing the movement of Ca2+ out of the vacuole were identified at physiological conditions of pH, vacuolar membrane potential, and ...

We report here that L-type Ca2+ channels activate rapidly in myotubes expressing current at high density and slowly in myotubes expressing current at low density. Partial block of the current in individual cells does not slow activation, indicating that Ca2+ influx does not link activation rate to current density. Activation rate is positively correlated ...

1. The quaternary derivative of the potent verapamil-analogue, (-)-D888, (qD888, 4-cyano-4-(3,4-dimethoxyphenyl)-N-[2-(3-methoxy phenyl)ethyl]-N,N,5-trimethyl-1-hexanaminium) was synthesized as a novel membrane-impermeable probe to study the localization of phenylalkylamine (PAA) effector domains on L-type Ca2+ channels. Channel block by qD888 was investigated in smooth ...

1. The quaternary derivative of the potent verapamil-analogue, (-)-D888, (qD888, 4-cyano-4-(3,4-dimethoxyphenyl)-N-[2-(3-methoxy phenyl)ethyl]-N,N,5-trimethyl-1-hexanaminium) was synthesized as a novel membrane-impermeable probe to study the localization of phenylalkylamine (PAA) effector domains on L-type Ca2+ channels. Channel block by qD888 was investigated in smooth ...

Ca²⁺ mediates the functional coupling between L-type Ca²⁺ channel (LTCC) and sarcoplasmic reticulum (SR) Ca²⁺ release channel (ryanodine receptor, RyR), participating in key pathophysiological processes. This crosstalk manifests as the orthograde ...

During skeletal muscle excitation-contraction (EC) coupling, membrane depolarizations activate the sarcolemmal voltage-gated L-type Ca²⁺ channel (Ca_V1.1). Ca_V1.1 in turn triggers opening of the sarcoplasmic ...

Hearts from subjects with different ages have different Ca(2+) signaling. Release of Ca(2+) from intracellular stores in response to an action potential initiates cardiac contraction. Both depolarization-stimulated and spontaneous Ca(2+) releases, Ca(2+) transients and Ca(2+) sparks, ...

Ca²⁺ signals in cardiac muscle cells are composed of spatially limited elementary events termed Ca²⁺ sparks. Several studies have also indicated that Ca²⁺ signals smaller than Ca²⁺ sparks can be elicited. These signals have ...

1. The processes that remove Ca2+ rapidly from the cytoplasm were studied in isolated rat ventricular myocytes subjected to whole-cell voltage clamp and internal perfusion with the Ca2+ indicator, indo-1. Na(+)-Ca2+ exchange was eliminated in most experiments by removing Na+ both internally and externally. 2. When the ...

We studied the permeation properties of two distinct single voltage-gated Ca²⁺ channels in bullfrog saccular hair cells to assess the roles of the channels as physiological Ca²⁺ transporters and multi-ion pores. By varying the permeant ions (Ba²⁺, ...

L-type Ca(2+) channels play a key role in the integration of physiological signals regulating insulin secretion that probably requires their localization to specific subdomains of the plasma membrane. We investigated the role of the intracellular II-III loop domains of the L-type channels Ca(v)1.2 and 1.3 in coupling of ...

Phospholemman (PLM), a member of the FXYD family of regulators of ion transport, is a major sarcolemmal substrate for protein kinases A and C in cardiac and skeletal muscle. In the heart, PLM co-localizes and co-immunoprecipitates with Na⁺-K⁺-ATPase, Na⁺/Ca²⁺ exchanger and L-type ...

1. The action of mibefradil was studied on wild type class A calcium (Ca2+) channels and various class A/L-type channel chimaeras expressed in Xenopus oocytes. The mechanism of Ca2+ channel block by mibefradil was evaluated with two microelectrode voltage clamp. 2. Resting-state dependent block (or initial block) of barium currents ...

The action of mibefradil was studied on wild type class A calcium (Ca²⁺) channels and various class A/L-type channel chimaeras expressed in Xenopus oocytes. The mechanism of Ca²⁺ channel block by mibefradil was evaluated with two microelectrode voltage clamp.Resting-state dependent block ...

Two ampullary epithelial properties necessary for electroreception were used to identify the types of ion channels and transporters found in apical and basal membranes of ampullary receptor cells of skates and to assess their individual role under voltage-clamp conditions. The two essential properties are (1) a steady-state negative conductance generated in apical membranes and (2) a small, ...

This study was designed to examine the effect of infrasound exposure (5 Hz at 130 dB) on whole-cell L-type Ca2+ currents (WLCC) in rat ventricular myocytes and the underlying mechanism(s) involved. Thirty-two adult Sprague-Dawley rats were randomly assigned to infrasound exposure and control groups. [Ca2+](i), WLCC, mRNA expression of ...

In some forms of cardiac hypertrophy and failure, the gain of Ca(2+)-induced Ca(2+) release [CICR; i.e., the amount of Ca(2+) released from the sarcoplasmic reticulum normalized to Ca(2+) influx through L-type Ca(2+) channels (LTCCs)] decreases despite the normal whole cell ...

Glutathionylation as a posttranslational modification of proteins is becoming increasingly recognized, but its role in many diseases has not been demonstrated. Oxidative stress and alterations in calcium homeostasis are associated with the development of cardiac hypertrophy. Because the cardiac L-type Ca(2+) channel can be persistently activated after ...

The skeletal muscle L-type Ca(2+) channel or dihydropyridine(DHP)-sensitive receptor is a key molecule involved in membrane voltage-sensing, sarcoplasmic reticulum Ca(2+) release, and muscle contraction. Previous work from our laboratory has shown that the insulin-like growth factor-1 (IGF-1) increases skeletal muscle ...

The aim of the present study was to investigate the effects of 2,5-di-t-butyl-1,4-benzohydroquinone (BHQ), an inhibitor of the sarco-endoplasmic reticulum Ca²⁺-ATPase (SERCA), on the whole-cell voltage-dependent L-type Ca²⁺ current (I_Ca(L)) of ...

Although long-term potentiation (LTP) has been intensely studied, there is disagreement as to which molecules mediate and modulate LTP. This is partly due to the presence of mechanistically distinct forms of LTP that are induced by different patterns of stimulation and that depend on distinct Ca²⁺ sources. Here we report a novel role for the arachidonic ...

Abnormal mechanical load, as seen in hypertension, is found to induce heart cell apoptosis, yet the signaling link between cell stretch and apoptotic pathways is not known. Using an in vitro stretch model mimicking diastolic pressure stress, here we show that Ca(2+) signaling participates essentially in the early stage of stretch-induced apoptosis. In neonatal rat ...

Hyperosmotic stress promotes rapid and pronounced apoptosis in cultured cardiomyocytes. Here, we investigated if Ca(2+) signals contribute to this response. Exposure of cardiomyocytes to sorbitol [600 mosmol (kg water)(-1)] elicited large and oscillatory intracellular Ca(2+) concentration increases. These Ca(2+) signals were inhibited ...

The L-type Ca current (I_Ca,L), essential for normal cardiac function, also regulates dynamic action potential (AP) properties that promote ventricular fibrillation. Blocking I_Ca,L can prevent ventricular fibrillation, but only at levels suppressing contractility. We speculated that, instead ...

Acute oxygen sensing in the heart is thought to occur through redox regulation and phosphorylation of membrane channels. Here we report a novel O₂-sensing mechanism involving the C-terminus of the L-type Ca²⁺ channel and regulated by PKA phosphorylation. In patch-clamped myocytes, oxygen deprivation decreased ...

Ghrelin is an endogenous growth hormone secretagogue (GHS) causing release of GH from pituitary somatotropes through the GHS receptor. Secretion of GH is linked directly to intracellular free Ca(2+) concentration ([Ca(2+)]i), which is determined by Ca(2+) influx and release from intracellular Ca(2+) storage sites. ...

The L-type Ca channel agonist FPL 64176 increased the amplitude of both Ca currents and Ca transients elicited from isolated voltage clamped rat ventricular myocytes far more than it increased the rate of rise of the Ca transients. Consequently, the gain function relating the amplitude of peak ...

Cell swelling-induced insulin secretion represents an alternative pathway of stimulation of insulin secretion. INS-1E rat tumor beta cells do not release insulin in response to cell swelling in presence of Ca(2+) despite a good response to glucose challenge and appropriate increase in cell volume. Surprisingly, perifusion with Ca(2+)-depleted medium showed ...

Endogenous adenosine has already been shown to inhibit transmitter release from the rod synapse by suppressing Ca(2+) influx through voltage-gated Ca(2+) channels. However, it is not clear how adenosine modulates the cone synapse. Cone photoreceptors, like rod photoreceptors, also possess L-type Ca(2+) channels ...

We present a probability density approach to modeling localized Ca2+ influx via L-type Ca2+ channels and Ca2+-induced Ca2+ release mediated by clusters of ryanodine receptors during excitation-contraction coupling in cardiac myocytes. Coupled advection-reaction equations are derived relating ...

The superficial (tonic) abdominal flexor muscles of Atya lanipes do not generate Ca(2+) action potentials when depolarized and have no detectable inward Ca(2+) current. These fibers, however, are strictly dependent on Ca(2+) influx for contraction, suggesting that they depend on Ca(2+)-induced ...

Memory shows age-related decline. According to the current prevailing theoretical model, encoding of memories relies on modifications in the strength of the synapses connecting the different cells within a neuronal network. The selective increases in synaptic weight are thought to be biologically implemented by long-term potentiation (LTP). Here, we report that tetanic stimulation of afferent ...

AimsCardiac L-type Ca²⁺-currents show distinct alterations in chronic heart failure, including increased single-channel activity and blunted adrenergic stimulation, but minor changes of whole-cell currents. Expression of L-type Ca²⁺-channel ?₂-subunits is enhanced in ...

? Rotundifolone is the major constituent of the essential oil of Mentha x villosa Hudson. In preliminary studies, rotundifolone induced significant hypotensive, bradycardic and vasorelaxant effects in rats. Thus, to gain more insight into the pharmacology of rotundifolone, the aim of this study was to characterize the molecular mechanism of action involved in relaxation produced by rotundifolone. ...

1. The functional coupling of beta(2)-adrenoceptors (beta(2)-ARs) to murine L-type Ca(2+) current (I(Ca(L))) was investigated with two different approaches. The beta(2)-AR signalling cascade was activated either with the beta(2)-AR selective agonist zinterol (myocytes from wild-type mice), or by spontaneously active, unoccupied ...

Somatostatin (somatotropin release-inhibiting factor [SRIF]) is known to modulate the excitability of retinal ganglion cells, but the membrane mechanisms responsible and the extent to which intracellular calcium signaling is affected have not been determined. We show that somatostatin receptor subtype 4 (sst(4)) is expressed specifically in rat ganglion cells and that the generation of repetitive ...

BACKGROUND: -Chronic iron-overload (CIO) is associated with blood disorders such as thalassemias and hemochromatosis. A major prognostic indicator of survival in patients with CIO is iron-mediated cardiomyopathy, characterized by contractile dysfunction and electrical disturbances including slow heart rate (HR; bradycardia) and heart block. METHODS AND RESULTS: -We have used a mouse model of CIO ...

To investigate Ca(2+) dynamics in earlier phases of follicular development we compared the resting [Ca(2+)](i) and tested the functional responses to agonist/antagonist of L-type voltage-operated calcium channels (VOCCs) in small follicles GCs from hens during oviposition (O-GCs) and forced molt (M-GCs), using the microspectrofluorimetric ...

BackgroundThe ability to establish human induced pluripotent stem cells (hiPSCs) by reprogramming of adult fibroblasts and to coax their differentiation into cardiomyocytes opens unique opportunities for cardiovascular regenerative and personalized medicine. In the current study, we investigated the Ca²⁺-handling properties of hiPSCs ...

The L-type Ca2+ channel (Ca(v)1.2) is the main pathway for trans-sarcolemmal (SL) Ca2+ influx in cardiac myocytes. To maintain Ca2+ homeostasis, chronic SL Ca(2+)-influx must be matched by chronic SL efflux. In this study we tested the hypothesis that chronic downregulation of SL ...

The Rem, Rem2, Rad, and Gem/Kir (RGK) GTPases, comprise a subfamily of small Ras-related GTP-binding proteins, and have been shown to potently inhibit high voltage-activated Ca²⁺ channel current following overexpression. Although the molecular mechanisms underlying RGK-mediated Ca²⁺ channel regulation remains ...

Objective:To investigate pharmacologically whether CaSRs are involved in the Ca²⁺ antagonist-induced [Ca²⁺]i elevation in gingival fibroblasts.Materials and Methods:Gin-1 cells, normal human gingival fibroblasts, were used as the material. The ...

Regulation of CaV1.2 channels in cardiac myocytes by the ?-adrenergic pathway requires a signaling complex in which the proteolytically processed distal C-terminal domain acts as an autoinhibitor of channel activity and mediates up-regulation by the ?-adrenergic receptor and PKA bound to A-kinase anchoring protein 15 (AKAP15). We examined the significance of this distal ...

Invertebrate L-type calcium channel, LCa(v) 1, isolated from the pond snail Lymnaea stagnalis is nearly indistinguishable from mammalian Ca(v) 1.2 (?1C) calcium channel in biophysical characteristics observed in vitro. These L-type channels are likely constrained within a narrow range of biophysical parameters to perform similar functions in the snail and ...

The effects of myricetin (3,3',4',5,5',7-hesahydroxyflavone), a natural flavonoid found in edible plants, were studied on vascular smooth muscle L-type Ca(2+) channels by comparing its mechanical, radioligand binding, and electrophysiological properties to those of the Ca(2+) channel agonist (S)-(-)-Bay K 8644. In rat aorta rings, both ...

Exposing bovine chromaffin cells to a single 5 ns, high-voltage (5 MV/m) electric pulse stimulates Ca(2+) entry into the cells via L-type voltage-gated Ca(2+) channels (VGCC), resulting in the release of catecholamine. In this study, fluorescence imaging was used to monitor nanosecond pulse-induced effects on intracellular ...

The effects of trimebutine maleate (TM) on spontaneous contractions of colonic longitudinal muscle were investigated in guinea pigs. The contractile responses of smooth muscle strips were recorded by an isometric force transducer. Membrane and action potentials were detected by an intracellular microelectrode technique. The whole-cell patch clamp recording technique was used to record the changes ...

Alloxan is widely used to induce diabetes mellitus in experimental animals. Recent studies have provided evidence that alloxan has direct actions on cardiac muscle contraction. The aim of this study was to further investigate the mechanisms underlying the effects of alloxan on ventricular myocyte shortening and intracellular Ca(2+) transport. Amplitude of myocyte shortening ...

ObjectiveWe tested the hypothesis that hypoxia inhibits currents through L-type Ca²⁺ channels and inhibits norepinephrine-induced rises in intracellular Ca²⁺ in cremasteric arteriolar muscle cells, thus accounting for the inhibitory effect of hypoxia on norepinephrine-induced contraction of ...

L-type voltage-gated calcium channels (LTCCs) have long been considered as crucial regulators of neuronal excitability. This role is thought to rely largely on coupling of LTCC-mediated Ca(2+) influx to Ca(2+)-dependent conductances, namely Ca(2+)-dependent K(+) (K(Ca)) channels and nonspecific ...

We found that 3,4-diaminopyridine (3,4-DAP), a voltage-gated potassium channel (K(V)) inhibitor, elicits pH-sensitive periodic contractions (PCs) of coronary smooth muscles. Underlying mechanisms of PCs, however, remained to be elucidated. The present study was performed to examine the roles of ion channels in the genesis of PCs. To determine the electromechanical changes of smooth muscles, ...

AMPA receptor (AMPAR) plasticity at glutamatergic synapses in the mesoaccumbal dopaminergic pathway has been implicated in persistent cocaine-induced behavioral responses; however, the precise mechanism underlying these changes remains unknown. Utilizing cocaine psychomotor sensitization, we have examined phosphorylation of GluA1 at key residues serine 845 (S845) and S831, as well as GluA1 cell ...

Ca²⁺ channel inactivation in the neurons of the freshwater snail, Lymnaea stagnalis, was studied using patch-clamp techniques. In the presence of a high concentration of intracellular Ca²⁺ buffer (5 mM EGTA), the inactivation of these Ca²⁺ channels is entirely voltage ...

The novel alpha1D Ca2+ channel together with alpha1C Ca2+ channel contribute to the L-type Ca2+ current (I(Ca-L)) in the mouse supraventricular tissue. However, its functional role in the heart is just emerging. We used the alpha1D gene knockout (KO) mouse to investigate the electrophysiological features, the ...

In cardiac myocytes, excitation-contraction coupling depends upon sarcoplasmic reticular Ca²⁺ release triggered by Ca²⁺ influx through L-type Ca²⁺ channels. Although Na⁺-Ca²⁺ ...

Current through L-type calcium channels (Ca(V)1.2 or dihydropyridine receptor) can be blocked by micromolar concentrations of trivalent cations like the lanthanide gadolinium (Gd(3+)). It has been proposed that trivalent block is due to ions competing for a binding site in both the open and closed configuration, but possibly with different trivalent ...

Caenorhabditis elegans is a powerful model system widely used to investigate the relationships between genes and complex behaviors like locomotion. However, physiological studies at the cellular level have been restricted by the difficulty to dissect this microscopic animal. Thus, little is known about the properties of body wall muscle cells used for locomotion. Using in situ patch clamp ...

BACKGROUND: Diabetes and hypertension have significant effects on cardiac calcium (Ca(2+)) regulation, which plays an essential role in determining cardiac function. The effect of peroxisome proliferator-activated receptor (PPAR)-? agonists on Ca(2+) regulation in the cardiomyocytes is unclear. OBJECTIVE: The purpose of this study was to investigate the ...

Ionic currents were investigated by a patch clamp technique in a clonal strain of pituitary (GH3) cells, using the whole cell configuration with Cs+ internal solution. Depolarizing pulses positive to 0 mV from a holding potential of -50 mV activated the voltage-dependent L-type Ca2+ current (ICa,L) and late outward current. Upon repolarization to the ...

Muscarinic acetylcholine receptor (mAChR) activation of pancreatic ?-cells elevates intracellular Ca(2+) and potentiates glucose-stimulated insulin secretion. In addition, it activates a number of signaling molecules, including ERK1/2, whose activation has been shown to play an important role in regulating pancreatic ?-cell function and mass. The aim of this work was to ...

1. The mechanisms of action of semotiadil fumarate, a novel Ca2+ antagonist, were examined by measuring the cytosolic Ca2+ level ([Ca2+]i) and force of contraction in porcine coronary arteries, and by determining [3H]-pyrilamine binding to bovine cerebellar membranes. 2. Semotiadil or verapamil (0.1 and 1 microM) inhibited both the ...

Curine is a novel bisbenzylisoquinoline alkaloid that has previously been reported as a vasodilator. The underlying mechanism(s) of the vasodilator effect of curine remains to be characterized. In this study, we investigated the cellular mechanism that is responsible for the vasodilator effect of curine in the rat aorta. The vasorelaxant activity of curine was recorded using a myograph. ...

The physiological role of the cystic fibrosis transmembrane conductance regulator (CFTR) in cardiomyocytes remains unclear. Using spontaneously beating neonatal ventricular cardiomyocytes from wild-type (WT) or CFTR knockout (KO) mice, we examined the role of CFTR in the modulation of cardiomyocyte contraction rate. Contraction rates of spontaneously beating myocytes were captured by video ...

"Spontaneous" Ca2+ sparks and ryanodine receptor type 3 (RyR3) expression are readily detected in embryonic mammalian skeletal muscle but not in adult mammalian muscle, which rarely exhibits Ca2+ sparks and expresses predominantly RyR1. We have used confocal fluorescence imaging and systematic sampling of enzymatically dissociated single striated muscle ...

Redox-dependent migration and proliferation of vascular smooth muscle cells (SMCs) are central events in the development of vascular proliferative diseases; however, the underlying intracellular signaling mechanisms are not fully understood. We tested the hypothesis that activation of Nox1 NADPH oxidase modulates intracellular calcium ([Ca(2+)](i)) levels. Using cultured SMCs ...

Sudden cardiac death remains one of the most prevalent modes of death and is mainly caused by ventricular fibrillation (VF) in the setting of acute ischemia resulting from coronary thrombi. Animal experiments have shown that platelet activation may increase susceptibility of ischemic myocardium to VF, but the mechanism is unknown. In the present study, we evaluated the effects of activated blood ...

L-type Ca(2+) channels (LTCCs) play a critical role in Ca(2+)-dependent signaling processes in a variety of cell types. The number of functional LTCCs at the plasma membrane strongly influences the strength and duration of Ca(2+) signals. Recent studies demonstrated that endosomal trafficking provides a mechanism ...

Cochlear inner hair cells (IHCs) release neurotransmitter onto afferent auditory nerve fibers in response to sound stimulation. Normal development and function of inner hair cells require the expression of alpha subunit 1.3 forming L-type voltage-gated Ca(2+) channel (Ca(V)1.3). Here, we used immunohistochemistry and reverse ...

Evidence accumulated over more than two decades has implicated Ca²⁺ dysregulation in brain aging and Alzheimer's disease (AD), giving rise to the Ca²⁺ hypothesis of brain aging and dementia. Electrophysiological, imaging, and behavioral studies in hippocampal or cortical neurons of rodents and rabbits have ...

The strange quark helicity distribution ?s(x) was derived at LO from the inclusive asymmetry Aa, d and the semi-inclusive asymmetries A1, d?+, A1, d?-, A1, dK+, A1, ...

Experimental data on the unsteady aerodynamics of oscillating airfoils ... instrumentation cables a1.d clearance for the push-pull rods were included in ..... part is to choose the appropriate family of smooth curves. ...

... SSUBJECT: Report of USATECOM Project No 1F-3216-42, Evaluation of Computer, Ballistic, M13AID, with Improved Illumination for M60 Series ...

Surface Management System. " How Technology Improves Operations at SDF ... How Technology is Improving Operations @ SDF ...

channels with verapamil also reduced the effect. These results suggest that 5-HT3R activation, coupledM (Sigma); LY-278,584, 1 lm (Sigma); verapamil, 20 lM (Sigma); 2-methyl-5-hydroxytryptamine maleate (2-M-5,584 5-HT3R �440 � 150* �1.10 �.17* �2.4 � 1.4* Verapamil L-type Ca2+ channels �250 � 70 �0.80 �.001* �1

of verapamil (109% 19% of baseline, n 5; pcific VDCCs to STDP induction. L-type Ca2 channels (L-VDCCs) have of Ni2 antagonist verapamil (50 M) blocked spike timing- dependent LTP at thalamic afferents (95% 14 LTPbaseline, n 5; Figure 5A). Verapamil did not affect presynaptic release as assessed by three stimulations

of the expressed channels was observed afterA-kinase anchoring protein called AKAP79. In trans- increases in cAMP (Yoshida et al., 1992; Yatani et al.,fected cells expressing a mutant AKAP79 that is un- 1995). Thus have shown that the 1Ction of an AKAP with PKA was required for -adrener- subunit is a substrate

Studying depolarisation induced calcium entry in our recently developed in situ lung slice model for molecular live cell imaging of selectively visualised pulmonary neuroepithelial bodies (NEBs), exemplified the need for information on the localisation of voltage-gated calcium channels (Ca(v)) in lungs in general, and related to sensory airway receptors more specifically. The ...

In the heart, L-type voltage dependent calcium channels (L-VDCC) provide Ca(2+) for the activation of contractile apparatus. The best described pathway for L-type Ca(2+) current (I(Ca,L)) modulation is the phosphorylation of calcium channels by cAMP-dependent protein kinase A (PKA), the activity of which is ...

A major clinical problem encountered with the use of non-steroidal anti-inflammatory drugs (NSAIDs) is gastrointestinal complications. We have previously suggested that both decreases in prostaglandin E(2) (PGE(2)) levels and mucosal apoptosis are involved in the development of NSAID-produced gastric lesions and that this apoptosis is mediated by an increase in the intracellular ...

Effects of haloperidol on L-type CaV1.2 channel were studied. Calcium current was measured in whole cell patch-clamp using calcium as a charge carrier. Inhibition by haloperidol was investigated in CaV1.2 channel natively expressed in rat cardiac myocytes and recombinant cardiac (CaV1.2a) and vascular (CaV1.2b) ...

To minimize the effects of Ca2+ buffering and signaling, this study sought to examine single Ca2+ channel properties using Sr2+ ions, which substitute well for Ca2+ but bind weakly to intracellular Ca2+ buffers. Two single-channel fluctuations were distinguished by their sensitivity to dihydropyridine agonist ...

Calcitonin gene-related peptides (CGRP) and adrenomedullin (ADM) belong to the calcitonin family of peptides and are structurally related. Both peptides are found in the neurons of the CNS and play a role in many neuronal functions, including the control of blood pressure. The nucleus tractus solitarius (NTS) is known to play a major role in the regulation of cardiovascular, respiratory, ...

Neokyotorphin [TSKYR, hemoglobin alpha-chain fragment (137-141)] has previously been shown to enhance fibroblast proliferation, its effect depending on cell density and serum level. Here we show the dependence of the effect of neokyotorphin on cell type and its correlation with the effect of protein kinase A (PKA) activator 8-Br-cAMP, but not the PKC activator 4beta-phorbol 12-myristate, ...

Calcium ions are crucial elements of excitation-contraction coupling in cardiac myocytes. The intracellular Ca(2+ ) concentration changes continously during the cardiac cycle, but the Ca(2+ ) entering to the cell serves as an intracellular second messenger, as well. The Ca(2+ ) as a second messenger influences the activity of many ...

Calcium ion (Ca2+) is one of the key regulatory elements for ciliary movements in the Paramecium species. It has long been known that members of Paramecium species including green paramecia (Paramecium bursaria) exhibit galvanotaxis which is the directed movement of cells toward the anode by swimming induced in response to an applied voltage. However, our knowledge on the mode ...

Visnadine, an active principle extracted from the fruit of Ammi visnaga, exhibits peripheral and coronary vasodilator activities and has been used for the treatment of angina pectoris. The present study was undertaken to further characterize the inhibitory effects of visnadine on the contractile responses in rat isolated aortic rings and portal vein segments. Visnadine (< 10(-5) M) selectively ...

The goal of systems biology is to relate events at the molecular level to more integrated scales from organelle to cell, tissue, and living organism. Here, we review how normal and abnormal excitation-contraction coupling properties emerge from the protein scale, where behaviors are dominated by randomness, to the cell and tissue scales, where heart has to beat with reliable regularity for a ...

The role of intracellular organelles in Ca²⁺ homeostasis was studied in salamander rod and cone photoreceptors under conditions that simulate photoreceptor activation by darkness and light. Sustained depolarization evoked a Ca²⁺ gradient between the cell body and ellipsoid regions of the inner segment (IS). The ...