Dries et al. show that injured myocardial slices from the subendocardium are more susceptible to spontaneous Ca2+ release events and whole-slice contractions than those from the subepicardium, and that this is reduced by CaMKII inhibition.

The cardiac KCNQ1 channel is a promising anti-arrhythmic target. Yazdi et al. report on how PUFAs interact with two binding sites in KCNQ1 to trigger channel activation. These findings further our mechanistic understanding of how to modulate KCNQ1 activity.

Scellini et al. show that mavacamten, a preclinical inhibitor of sarcomeric myosins, has a fast and reversible mechanical action on skeletal and cardiac myofibers that is mediated by a shift of motor heads out of a force-generating cycle, with no effect on the kinetics of cardiac force development.

Rasicci et al. investigate the mechanochemical properties of distinct isoforms of cardiac myosin carrying the K104E regulatory light chain mutation, previously associated with hypertrophic cardiomyopathy. They demonstrate that the mutation does not affect the ATPase or motor properties of human cardiac myosin subfragment-1 (M2β-S1), but the mutation increases the sliding velocity and disrupts RLC incorporation in full-length α-cardiac myosin.

Clippinger et al. examine a mutation in troponin T that causes hypertrophic cardiomyopathy and demonstrate that increased molecular mechanics drive the early disease pathogenesis, leading to secondary activation of mechanobiological signaling pathways.

Acid-sensing ion channels (ASIC) play central roles in the central and peripheral nervous systems. In this paper, Chen et al. show that changes to a single arginine of a human ASIC both affect the efficacy of proton-mediated gating and delay the desensitization of the channel.

Fazlollahi et al. show that contraction and relaxation remain tightly coupled in intact canine myocardium after exercise training and/or myocardial infarction. They postulate that the action of cardiac myosin binding protein C on actin and myosin may play a key role in this process.