Bioelectric signaling regulates size in zebrafish fins.

The scaling relationship between the size of an appendage or organ and that of the body as a whole is tightly regulated during animal development. If a structure grows at a different rate than the rest of the body, this process is termed allometric growth. The zebrafish another longfin (alf) mutant shows allometric growth resulting in proportionally enlarged fins and barbels.

A common structural component for β-subunit mediated modulation of slow inactivation in different KV channels.

Background/aims: Potassium channels are tetrameric proteins providing potassium selective passage through lipid embedded proteinaceous pores with highest fidelity. The selectivity results from binding to discrete potassium binding sites and stabilization of a hydrated potassium ion in a central internal cavity. The four potassium binding sites, generated by the conserved TTxGYGD signature sequence are formed by the backbone carbonyls of the amino acids TXGYG.

Coxsackievirus B3 modulates cardiac ion channels.

Infections with coxsackieviruses of type B (CVBs), which are known to induce severe forms of acute and chronic myocarditis, are often accompanied by ventricular arrhythmias and sudden cardiac death. The mechanisms underlying the development of virus-induced, life-threatening arrhythmias, which are phenotypically similar to those observed in patients having functionally impaired cardiac ion channels, remain, however, enigmatic. In the present study, we show, for the first time, modulating time-dependent effects of CVB3 on the cardiac ion channels KCNQ1, hERG1, and Cav1.

Overlapping cardiac phenotype associated with a familial mutation in the voltage sensor of the KCNQ1 channel.

Background: Cardiac action potential repolarisation is determined by K(+) currents including I(Ks). I(Ks) channels are heteromeric channels composed of KCNQ1 and KCNE E-subunits. Mutations in KCNQ1 are associated with sinus bradycardia, familial atrial fibrillation (fAF) and/or short QT syndrome as a result of gain-of-function, and long QT syndrome (LQTS) due to loss-of-function in the ventricles.

Tracking a complete voltage-sensor cycle with metal-ion bridges.

Voltage-gated ion channels open and close in response to changes in membrane potential, thereby enabling electrical signaling in excitable cells. The voltage sensitivity is conferred through four voltage-sensor domains (VSDs) where positively charged residues in the fourth transmembrane segment (S4) sense the potential. While an open state is known from the Kv1.

Modulation of human ether a gogo related channels by CASQ2 contributes to etiology of catecholaminergic polymorphic ventricular tachycardia (CPVT).

Rationale: The plateau phase of the ventricular action potential is the result of balanced Ca(2+) influx and K(+) efflux. The action potential is terminated by repolarizing K(+) currents. Under β-adrenergic stimulation, both the Ca(2+)-influx and the delayed rectifier K(+) currents I(K) are stimulated to adjust the cardiac action potential duration to the enhanced heart rate and to ascertain adequate increase in net Ca(2+) influx.

The activation of the rat insulin gene II by BETA2 and PDX-1 in rat insulinoma cells is repressed by Pax6.

The transcriptional transactivator Pax6 binds the pancreatic islet cell-specific enhancer sequence (PISCES) of the rat insulin I gene. However the human, mouse, and rat insulin gene II promoters do not contain a PISCES element. To analyze the role of Pax6 in those PISCES-less promoters, we investigated its influence on rat insulin gene II expression and included in our studies the main activators: pancreatic and duodenal homeobox protein-1 (PDX-1) and BETA2/E47.

Long QT syndrome-associated mutations in the voltage sensor of I(Ks) channels.

The plateau phase of the ventricular action potential is the result of balanced Ca2+ influx and K+ efflux. The action potential is finally terminated by repolarising K+ currents. Under beta-adrenergic stimulation the slowly activating component of the human cardiac delayed rectifier K+ current I(Ks) provides the major repolarising component.

Serum- and glucocorticoid-inducible kinases (SGK) regulate KCNQ1/KCNE potassium channels.

The stress reaction includes the release of stress hormones such as cortisol via the HPA axis4. One of the genes regulated by cortisol is the serum- and glucocorticoid-inducible kinase 1 (SGK1) a stimulator of the slow outward potassium channel KCNQ1/KCNE1-one of the major mediators of cardiac repolarization. Apart from KCNE1, several other KCNE beta subunits including KCNE3 and KCNE5 have been detected at the mRNA level in cardiac tissue as well as in the inner ear and the gastro-intestinal tract.

Differential modulation of cardiac potassium channels by Grb adaptor proteins.

Scaffolding growth factor receptor-bound (Grb) adaptor proteins are components of macromolecular signaling complexes at the plasma membrane and thus are putative regulators of ion channel activity. The present study aimed to define the impact of Grb adaptor proteins on the function of cardiac K(+) channels. To this end channel proteins were coinjected with the adaptor proteins in Xenopus oocytes and channel activity analyzed with two-electrode voltage-clamp.

Long QT syndrome-associated mutations in KCNQ1 and KCNE1 subunits disrupt normal endosomal recycling of IKs channels.

Physical and emotional stress is accompanied by release of stress hormones such as the glucocorticoid cortisol. This hormone upregulates the serum- and glucocorticoid-inducible kinase (SGK)1, which in turn stimulates I(Ks), a slow delayed rectifier potassium current that mediates cardiac action potential repolarization. Mutations in I(Ks) channel alpha (KCNQ1, KvLQT1, Kv7.

A schizophrenia-linked mutation in PIP5K2A fails to activate neuronal M channels.

Rationale: Evidence for an association between phosphatidylinositol-4-phosphate 5-kinase II alpha (PIP5K2A) and schizophrenia was recently obtained and replicated in several samples. PIP5K2A controls the function of KCNQ channels via phosphatidylinositol-4,5-bisphosphate (PIP2) synthesis. Interestingly, recent data suggest that KCNQ channels suppress basal activity of dopaminergic neurons and dopaminergic firing.