Issues

JGP study reveals that the membrane lipid PI(4,5)P₂ alters the activity of Na_V1.4 channels by modulating their gating behavior.

Light-controlled availability for phosphorylation reveals dominant roles of select R-domain serines in CFTR channel activation.

Combining machine learning with mechanistic computational modeling is enabling the discovery of novel genotype-phenotype relationships in heart disease.

Glycine-gated NMDA receptors contribute to brain functions and disorders. Rouzbeh et al. shed light on their odd pharmacology.

GluN1/GluN3 receptors display unusual activation properties compared to GluN1/GluN2 NMDA receptors. This study investigates mechanisms by which GluN1-selective antagonists potentiate GluN1/GluN3 responses and shows that variation in GluN1 agonist binding domain conformations promoted by antagonist binding differently modulates agonist potency and efficacy at GluN3 subunits.

This work identifies a binding motif in a serotonin channel (5-HT_3A) for RIC-3 protein. The discovery positions the interaction as a potential drug target in treating 5-HT_3A-related disorders and opens new research directions to understand channel biogenesis.

Na_V channel gating is highly regulated to generate and support action potential firing in excitable tissues. In this study, optogenetic-activation of phosphoinositide-phosphatases reveals that PI(4,5)P₂ levels at the membrane tune the physiological gating behavior of Na_V1.4 channels.

Expression of N-terminal truncated cMyBPC is sufficient to modulate systolic function in vivo, demonstrating that these domains have an important functional role. Understanding of region-specific function of cMyBPC can be leveraged to manipulate various aspects of cardiac function.

The intracellular C-terminal positively charged regions of the γ subunits play important roles in BK channel modulation. This work identifies positively charged peptides as BK channel modulators and reveals a role for the Ca²⁺-bowl site in BK channel modulation by positively charged peptides and the auxiliary γ subunits.

Diastolic dysfunction was induced in guinea pigs by pressure overload. We found myofilament dysfunction that included depressed force development, reduced tension-dependent ATP consumption rate, prolonged K_tr, and prolonged myofibril relaxation in the absence of a change in myosin isoform composition. Blunted cross-bridge cycle kinetics may be an important contributor to diastolic heart failure.

Characterization of stretch-activated currents from dorsal root ganglion neurons reveals heterogeneity at the single-channel conductance level and suggests that in addition to PIEZO2, at least two other mechanically activated ion channels are expressed in somatosensory neurons.