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 NaV1.5 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.
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.
Distinct lipid bilayer compositions have general and protein-specific effects on K+ channel function
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.
Phenanthrene impacts zebrafish cardiomyocyte excitability by inhibiting IKr and shortening action potential duration
Kompella et al. show that the petroleum-derived pollutant phenanthrene blocks the zebrafish native ERG orthologue mediating IKr, thus suppressing outward protective currents initiated by premature beats and increasing the susceptibility to arrhythmia triggers.