Inhibition of voltage-gated Na currents by eleclazine in rat atrial and ventricular myocytes.

Background: Atrial-ventricular differences in voltage-gated Na currents might be exploited for atrial-selective antiarrhythmic drug action for the suppression of atrial fibrillation without risk of ventricular tachyarrhythmia. Eleclazine (GS-6615) is a putative antiarrhythmic drug with properties similar to the prototypical atrial-selective Na channel blocker ranolazine that has been shown to be safe and well tolerated in patients.

Objective: The present study investigated atrial-ventricular differences in the biophysical properties and inhibition by eleclazine of voltage-gated Na currents.

A Novel Mechanism for Calmodulin-Dependent Inactivation of Transient Receptor Potential Vanilloid 6.

The paralogues TRPV5 and TRPV6 belong to the vanilloid subfamily of the transient receptor potential (TRP) superfamily of ion channels, and both play an important role in overall Ca homeostasis. The functioning of the channels centers on a tightly controlled Ca-dependent feedback mechanism in which the direct binding of the universal Ca-binding protein calmodulin (CaM) to the channel's C-terminal tail is required for channel inactivation. We have investigated this interaction at the atomic level and propose that under basal cellular Ca concentrations CaM is constitutively bound to the channel's C-tail via CaM C-lobe only contacts.

Atrial-ventricular differences in rabbit cardiac voltage-gated Na currents: Basis for atrial-selective block by ranolazine.

Background: Class 1 antiarrhythmic drugs are highly effective in restoring and maintaining sinus rhythm in atrial fibrillation patients but carry a risk of ventricular tachyarrhythmia. The antianginal agent ranolazine is a prototypic atrial-selective voltage-gated Na channel blocker but the mechanisms underlying its atrial-selective action remain unclear.

Objective: The present study examined the mechanisms underlying the atrial-selective action of ranolazine.

New pyrimido-indole compound CD-160130 preferentially inhibits the KV11.1B isoform and produces antileukemic effects without cardiotoxicity.

KV11.1 (hERG1) channels are often overexpressed in human cancers. In leukemias, KV11.