Issues

Many clinically used drugs block cardiac hERG potassium channels yet also enhance current under some conditions. Docken, Marquis et al. combine kinetic modeling, atomistic simulations, and voltage-clamp experiments to test the hypothesis that the antiarrhythmic drug nifekalant opens hERG gates while blocking, revealing a mechanism that may reduce arrhythmia risk.

In the cardiomyocytes of male two-hit mice, both increased passive sarcomere stiffness and diastolic crossbridge activity represent potential therapeutic targets for reducing cardiomyocyte diastolic stiffness; whereas in females, cardiomyocyte diastolic stiffness is predominantly driven by elevated passive sarcomere stiffness.

AMPA receptors are glutamate receptors specific to bilaterian animals with complex nervous systems. Wang et al. investigated the biophysical function, pharmacology, and kinetics of AMPA receptors from diverse bilaterians, uncovering convergent evolution on functional hallmarks, such as heteromerization and channel properties, throughout the AMPA receptor family.