McDonald et al. use permeabilized rodent left ventricular cardiac myocytes to study power generation during the ejection phase of the cardiac cycle. They show that cardiac myosin binding protein-C regulates sarcomere-loaded shortening, especially at high loads, seemingly, by modulating cross-bridge availability.

Comb jellies are the oldest animal lineage and are missing six of our eight voltage-gated K⁺ channel lineages. We show here that they independently evolved a functionally diverse suite of voltage-gated K⁺ channels from a single ancestral Shaker family lineage.

Intrinsic cardiomyopathy is an emerging cause of heart failure in Marfan syndrome. Kellermayer et al. show that the ratio between titin isoforms N2BA and N2B is biased toward N2BA, suggesting an adaptation mechanism to counter passive-stiffness changes manifested in the Marfan syndrome cardiac tissue.

Cholinergic interneurons of the nucleus accumbens have a critical role regulating depressive-like behavior. Medrihan et al. use monosynaptic cell tracing in a depression mouse model to determine the regions projecting to the nucleus accumbens’ cholinergic neurons and to show that projections from the ventral hippocampus were significantly reduced in depressed mice.

Vysma et al. develop a Ca²⁺ release model that reproduces store load–dependent release and Ca²⁺ waves in skinned ventricular myocytes. They find that substantial increases in SR Ca²⁺ release and Ca²⁺ waves take place when Ca²⁺ sparks become prolonged embers above a threshold SR [Ca²⁺].

Combining anatomically realistic reconstructions with Monte Carlo simulations, Thoreson et al. found that the complex architecture of invaginating rod photoreceptor synapses extends glutamate’s lifetime in the cleft, promoting integration between release events at the cost of quantal variability.

By molecular dynamics simulations and in silico electrophysiology, Şahin and Zachariae show how the lipid PIP2 opens the human TPC2 ion channel and that its ion selectivity is established by an interplay of key structural elements of the pore.