Issues

JGP study suggests that stretch activation of fast-contracting skeletal muscle fibers might increase muscle endurance by boosting force production during fatigue.

The comprehensive meta-analysis from Clerx and coauthors challenges long-standing assumptions about data interpretation, data comparison, and electrophysiological data used to develop models.

We present variability in reported midpoints of activation and inactivation for the cardiac fast sodium current, I_Na, show the correlation between these midpoints, and discuss possible experimental sources of variability.

We demonstrate that stretch-activated force production is maintained under fatiguing conditions, while calcium-activated force declines in fast-contracting skeletal muscle fibers. This suggests the physiological role of stretch activation is to mitigate the effects of fatigue on force production, which would increase muscle endurance.

Mutations in the GRIN2B gene, encoding the GluN2B subunit of NMDA receptors, are linked to neurodevelopmental disorders. We show that two variants disrupt nanoscale coupling between NMDA receptors and BK channels, revealing nanodomain dysfunction as a potential mechanism contributing to GRIN2B-associated pathophysiology.

Single-molecule imaging provides a high spatial resolution of fluorescent ATP binding to myosin within cardiac myofibrils. This is used to determine how cMyBP-C affects the reserve of cardiac myosins used to modulate force. Here, we study PKA phosphorylation and a haploinsufficiency-causing mutation from human tissue.

CTX, a peptide neurotoxin derived from the scorpion Leiurus quinquestriatus, occludes the pore of voltage gated K channels with 1:1 stoichiometry. CTX binding to shaker K channels is temperature sensitive in high external K⁺ but not in high external Na⁺, revealing a K⁺-specific enthalpy component.

The movement of gating charges across the membrane electric field in response to depolarization is the essence of the voltage-sensing mechanism gating voltage-dependent ion channels. Here, the authors unravel molecular mechanisms in a voltage-sensing domain, which govern the kinetics and voltage dependence of calcium channel activation.

This work bridges molecular disorder and biomechanical function, providing a new lens to understand dynamic control and dysfunction in cardiomyocyte contraction via an understanding of ABLIM1 and the complexities of its phosphorylation and interactions in the sarcomere.

The kinetics of processing of the ENaC were studied in rat kidney. Alterations in levels of aldosterone produced rapid changes in cleaved γENaC and αENaC, with slower changes in full-length forms of the subunits. A kinetic model describing the results is proposed.