Issues

Update from the Editor-in-Chief

JGP study reveals that insufficient reuptake of calcium into the sarcoplasmic reticulum underlies arrhythmogenic variations in cardiac calcium transients.

Treating multiple cells from a single animal as independent for statistical analysis is pseudoreplication and can result in bogus estimates of significance.

TRPV3 is a Ca²⁺-permeable cation channel implicated in skin health and other inflammatory conditions. Wang et al. explore the mechanism of acid regulation of TRPV3 and show that the acidic residues D641, E682, E689, and D727 are key for proton inhibition and sensitization of this channel.

Liang and Yang show that the activity of TMEM16F, a scramblase and ion channel, is regulated by intracellular pH in a Ca²⁺-dependent manner. The effects of pH in TMEM16F activity stem from competition between protons and Ca²⁺ for the main Ca²⁺-binding residues in the channel.

Fortenbach et al. use genetic deletion of the K⁺ channel K_v2.1 to quantitatively dissect the ionic mechanisms contributing to the dark current of vertebrate rod photoreceptors. Loss of K_v2.1 resulted in reduced dark current, depolarization, increased intracellular free Ca²⁺, disruption of normal inner segment structure, and progressive photoreceptor degeneration.

Ca²⁺ alternans can lead to T-wave alternans, a highly arrhythmogenic phenomenon. Through a thermodynamic analysis of the molecular mechanisms involved in generating Ca²⁺ alternans, Millet et al. concluded that Ca²⁺ alternans are produced by an incomplete replenishment of SR Ca²⁺ during tachycardia.

Lorenzini et al. describe the native phosphorylation sites of Na_V1.5 channels in mouse left ventricles. By analyzing expression and function of phosphosilent and phosphomimetic mutants, they identify phosphorylation hot spots regulating channel cell surface expression and gating.

Winterstein et al. use the natural diversity of small viral K⁺ channels to address the impact of phospholipid bilayer composition on channel function. Single-channel recordings reveal a stimulating effect of anionic phospholipids on channel conductance and protein-specific effects on gating.

Voltage-gated Na⁺ channels activate faster than K⁺ channels in excitable cells. Catacuzzeno et al. develop a model that shows how the dielectric properties of a divergent side chain produce this difference in speed.

Kompella et al. show that the petroleum-derived pollutant phenanthrene blocks the zebrafish native ERG orthologue mediating I_Kr, thus suppressing outward protective currents initiated by premature beats and increasing the susceptibility to arrhythmia triggers.