Sodium channels are organized in multiple pools with distinct biophysical properties and subcellular localization, but the role of these subpopulations is not well understood. Computational modeling predicts that intercalated disk-localized sodium channels with shifted steady-state activation and inactivation voltage dependence promote faster cardiac conduction.

Dantrolene, an inhibitor of the cardiac calcium release channel (RyR2), is a lead compound for stabilizing overactive RyR2 in heart failure. We find that dantrolene inhibition requires RyR2 association with FKBP12.6, which in turn depends on RyR2 phosphorylation at S2808.

Lehman and Rynkiewicz show that, in the absence of Ca²⁺, troponin-I causes tropomyosin to pivot over relatively fixed points on actin subunits, blocking myosin-head binding sites on actin and thereby causing muscle relaxation.

Lewis et al. investigate how training status influences relaxed myosin conformations known to play a role in skeletal muscle metabolism. Their findings indicate that individuals with moderate activity levels have a shift in the relaxed conformations of their type II myosin molecules, lowering the basal ATP consumption.

Szanto et al. provide data that support the idea that rearrangement of S6, including its rotation, may mediate the communication between the activation gate and the inactivation gate controlling slow inactivation in K_V channels.

Histone proteins are known to be elevated in circulation where they contribute to vascular dysfunction. However, many details regarding the mechanism of action are unknown. Here, the authors show that P2XR7 channel current is activated by extracellularly applied histone proteins in a heterologous expression system.

This work demonstrates that the opening of lateralize cardiac connexin-43 hemichannels, in the absence of a cardiac pathology, is still sufficient to alter cardiac membrane excitability and promote arrhythmias upon β-adrenergic cardiac stress.