The potassium channel accessory subunit KChIP2 associates with Kv4.2 channels in the cardiac myocyte and is involved in the regulation of the transient outward current (I(to)) during the early phase of repolarization of the action potential. As a first step to biophysically probe the mechanism of KChIP2, we have chemically synthesized its minimal isoform, ...

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 Ca(2+)-binding protein whose regulatory ...

The rapidly activating and inactivating voltage-dependent outward K⁺ (Kv) current, I_A, is widely expressed in central and peripheral neurons. I_A has long been recognized to play important roles in determining neuronal firing properties and regulating neuronal excitability. Previous work demonstrated that Kv4.2 and Kv4.3 ...

MiRP3, the single-span membrane protein encoded by KCNE4, is localized by immunofluorescence microscopy to the transverse tubules of murine cardiac myocytes. MiRP3 is found to co-localize with Kv4.2 subunits that contribute to cardiac transient outward potassium currents (I_to). Whole-cell, voltage-clamp recordings of human MiRP3 and Kv4.2 expressed in a ...

BACKGROUND AND PURPOSEThe compound NS5806 increases the transient outward current (I_to) in canine ventricular cardiomyocytes and slows current decay. In human and canine ventricle, I_to is thought to be mediated by K_V4.3 and various ancillary proteins, yet, the exact subunit composition of ...

Recent evidence shows that the auxiliary subunit KChIP2, which assembles with pore-forming Kv4-subunits, represents a new potential regulator of the cardiac calcium-independent transient outward potassium current (I(to)) density. In hypertrophy and heart failure, KChIP2 expression has been found to be significantly decreased. Our aim was to examine the ...

Redox imbalance elicited by oxidative stress contributes to pathogenic remodeling of ion channels that underlies arrhythmogenesis and contractile dysfunction in the failing heart. This study examined whether the expression of K(+) channels in the remodeled ventricle is controlled by the thioredoxin system, a principal oxidoreductase network regulating redox-sensitive proteins. Ventricular ...

Hypertrophied myocardium is associated with reductions in the transient outward K⁺ current (Ito) and expression of pore-forming Kv4.2/4.3 and auxiliary KChIP2 subunits. Here we show that KChIP2 mRNA and protein levels are dramatically decreased to 10% to 30% of control levels in the left ventricle of aorta-constricted rats in vivo and phenylephrine ...

The Ca(2+)-binding proteins KChIP1-4 (KChIP3 is also known as DREAM and calsenilin) act as auxiliary subunits for voltage-gated K(+) channels in the Kv4 family. Here we identify three splicing isoforms of rat KChIP2 with variable N-terminal peptides. The two longer isoforms, which contain the 32-amino acid peptide, produce larger increases in Kv4.3 protein level and current ...

We conducted a kinetic analysis of the voltage dependence of macroscopic inactivation (?_fast, ?_slow), closed-state inactivation (?_closed,inact), recovery (?_rec), activation (?_act), and deactivation (?_deact) of Kv4.3 channels expressed alone in Xenopus oocytes ...

Clinical trials and epidemiological studies have suggested that dietary fish oil (FO) supplementation can provide an anti-arrhythmic benefit in some patient populations. The underlying mechanisms are not entirely clear. We wanted to understand how FO supplementation (for 4 weeks) affected the action potential configuration/duration of ventricular myocytes, and the ionic mechanism(s)/molecular ...

Clinical trials and epidemiological studies have suggested that dietary fish oil (FO) supplementation can provide an anti-arrhythmic benefit in some patient populations. The underlying mechanisms are not entirely clear. We wanted to understand how FO supplementation (for 4 weeks) affected the action potential configuration/duration of ventricular myocytes, and the ionic mechanism(s)/molecular ...

Members of the K(+) channel-interacting protein (KChIP) family bind the distal N termini of members of the Shal subfamily of voltage-gated K(+) channel (Kv4) pore-forming (?) subunits to generate rapidly activating, rapidly inactivating neuronal A-type (I(A)) and cardiac transient outward (I(to)) currents. In heterologous cells, KChIP co-expression increases cell surface ...

Mitochondrial NADH:ubiquinone oxidoreductase (complex I) is a very large membrane protein complex with a central function in energy metabolism. Complex I from the aerobic yeast Yarrowia lipolytica comprises 14 central subunits that harbour the bioenergetic core functions and at least 28 accessory subunits. Despite progress in structure ...

At least two functionally distinct transient outward K⁺ current (I_to) phenotypes can exist across the free wall of the left ventricle (LV). Based upon their voltage-dependent kinetics of recovery from inactivation, these two phenotypes are designated �I_to,fast� (recovery time constants on the order of tens of milliseconds) ...

The prokaryotic and eukaryotic homologues of complex I (proton-pumping NADH:quinone oxidoreductase) perform the same function in energy transduction, but the eukaryotic enzymes are twice as big as their prokaryotic cousins, and comprise three times as many subunits. Fourteen core subunits are conserved in all complexes I, and are sufficient for catalysis - ...

Gating transitions in the K(V)4.3 N-terminal deletion mutant ?2-39 were characterized in the absence and presence of KChIP2b. We particularly focused on gating characteristics of macroscopic (open state) versus closed state inactivation (CSI) and recovery. In the absence of KChIP2b ?2-39 did not significantly alter the steady-state activation "a(4)" relationship or general CSI characteristics, but ...

Voltage-gated Na+ channel (VGSC) ? Subunits are not "auxiliary." These multi-functional molecules not only modulate Na+ current (I(Na)), but also function as cell adhesion molecules (CAMs)-playing roles in aggregation, migration, invasion, neurite outgrowth, and axonal fasciculation. ? subunits are integral members of VGSC signaling complexes at nodes of ...

The herpes simplex virus DNA polymerase consists of two subunits-a catalytic subunit and an accessory subunit, UL42, that increases processivity. Mutations affecting the extreme C terminus of the catalytic subunit specifically disrupt subunit interactions and ablate virus ...

Heart repair by stem cell treatment may involve life-threatening arrhythmias. Cardiac progenitor cells (CPCs) appear best suited for reconstituting lost myocardium without posing arrhythmic risks, being commissioned towards cardiac phenotype. In this study we tested the hypothesis that mobilization of CPCs through locally delivered Hepatocyte Growth Factor and Insulin-Like Growth Factor-1 to heal ...

Heart repair by stem cell treatment may involve life-threatening arrhythmias. Cardiac progenitor cells (CPCs) appear best suited for reconstituting lost myocardium without posing arrhythmic risks, being commissioned towards cardiac phenotype. In this study we tested the hypothesis that mobilization of CPCs through locally delivered Hepatocyte Growth Factor and Insulin-Like Growth Factor-1 to heal ...

The mitochondrial replication machinery in human cells includes the DNA polymerase gamma holoenzyme and the TWINKLE helicase. Together, these two factors form a processive replication machinery, a replisome, which can use duplex DNA as template to synthesize long stretches of single-stranded DNA. We here address the importance of the smaller, accessory B ...

... We have recently shown that human pol 6 consists of at least four subunits (Mo et. al., 2000, Liu et al., 2000, Liu et al., submitted). ...

Paf1C is a transcriptional cofactor that has been implicated in various transcription-associated mechanisms spanning initiation, elongation and RNA processing, and is important for multiple aspects of development in Arabidopsis. Our recent studies suggest Arabidopsis Paf1C is crucial for proper regulation of genes within H3K27me3-enriched chromatin, and that a protein named PHP may act as an ...

The alpha(1)-adrenoceptor as well as the AT(1)- and the ET(A)-receptor couple to G-proteins of the Galpha(q/11) family and contribute to the regulation of the transient outward K(+) current (I(to,f)) under pathological conditions such as cardiac hypertrophy or failure. This suggests an important role of Galpha(q/11)-signalling in the physiological regulation of I(to,f). Here, we investigate mice ...

Ca(v)2.1 (P/Q-type) channels possess a voltage-sensitive pore-forming alpha(1) subunit that can associate with the accessory subunits alpha(2)delta, beta and gamma. The primary role of Ca(v)2.1 channels is to mediate transmitter release from nerve terminals both in the central and peripheral nervous system. Whole-cell voltage-clamp ...

Mechanisms underlying K(v)4 (Shal type) potassium channel macroscopic (open state) inactivation and recovery are unknown, as are mechanisms by which KChIP2 isoforms modulate these two processes. In a recent study (Xenopus oocytes, 2 microelectrode voltage clamp) we demonstrated that: i) Partial deletion of the K(v)4.3 proximal N-terminal domain (?2-39; deletes N-terminal amino acids 2-39) not only ...

RationalemicroRNA (miR)-133a regulates cardiac and skeletal muscle differentiation and plays an important role in cardiac development. Because miR-133a levels decrease during reactive cardiac hypertrophy, some have considered that restoring miR-133a levels could suppress hypertrophic remodeling.ObjectiveTo prevent the �normal� down-regulation of miR-133a induced by an acute hypertrophic ...

Complete atrioventricular block (CAVB) and related ventricular bradycardia are known to induce ventricular hypertrophy and arrhythmias. Different animal models of CAVB have been established with the most common being the dog model. Related studies were mainly focused on the consequences on the main repolarizing currents in these species, i.e. IKr and IKs, with a limited time point kinetics ...

Figure 1: Multi-subunit structure of CaV1��2 channels. Legend: CaV1��2 channels are comprised of a main pore-forming 1 subunit together with accessory proteins that include beta and alpha2delta subunits and calmodulin. Some channel complexes also include a gamma subunit. From Xu X, ...

Chromatin remodeling complexes control the availability of DNA binding sites to transcriptional regulators. Two distinct conserved forms of the SWI/SNF class of complexes are characterized by the presence of specific accessory subunits. In Drosophila, the core Brahma complex associates either with Osa to form the BAP complex or with Bap170 and Bap180 to ...

Modern ?-proteobacteria are thought to be closely related to the ancient symbiont of eukaryotes, an ancestor of mitochondria. Respiratory complex I from ?-proteobacteria and mitochondria is well conserved at the level of the 14 "core" subunits, consistent with that notion. Mitochondrial complex I contains the core subunits, present in all species, and up ...

?6?2?3* acetylcholine receptors (AChRs) on dopaminergic neurons are important targets for drugs to treat nicotine addiction and Parkinson's disease. However, it has not been possible to efficiently express functional ?6?2?3* AChRs in oocytes or transfected cells. ?6/?3 subunit chimeras permit expression of functional AChRs and reveal that parts of the ?6 M1 transmembrane ...