Issues

JGP study reveals that a sodium channel mutant blocks fast inactivation downstream of inactivation particle binding, diverting the channel into an alternative open state.

Hanna et al. reveal that early, but not late, developmental cardiac FKBP12 deficiency leads to dilated cardiomyopathy in the adult heart.

The regulation of mitochondrial calcium and its role in regulating cell death.

Hanna et al. generate two conditional mouse models of embryonic loss of FKBP12 in cardiomyocytes. Their findings show a progressive development of dilated cardiomyopathy, cardiac oxidative stress, and calcium leak, and suggest a role for FKBP12 in embryonic cardiac muscle.

In this work, Liu and Bezanilla describe a voltage-gated sodium channel mutant that removes fast inactivation while the fast inactivation particle, the IFM motif, remains bound. This work indicates that fast inactivation requires further conformational changes in addition to IFM motif binding.

At synapses, NMDA receptors (NMDAR) convert presynaptically released glutamate into a synaptic signal. Here, He and Wollmuth define the impact of various environmental factors and GluN2 subunit composition on the efficiency of rapid glutamate-induced channel opening.

Apel et al. demonstrate that the calcium-binding protein S100A1 binds the N2A region of titin and that binding is regulated through calcium concentration and pH. Their work suggests that this interaction is a physiological sensor to regulate titin function in the muscle.

In this study, McIlvried, Del Rosario, and colleagues show that mechanisms of adaptive plasticity are engaged in mouse and human sensory neurons after sustained depolarization. This phenomenon is reversible and involves alterations of voltage-gated sodium channel currents.

Gupta et al. show that Pannexin 1 (PANX1) channels can function as both hexamers and heptamers, but that heptameric PANX1 shows higher conductance, longer mean open times, and supports greater ATP release and dye uptake. Structurally distinct mechanisms underlie C-tail cleavage and receptor-mediated PANX1 activation.

In this study, Beaudoin et al. investigate the structural effects of N-linked glycosylation on Na_V channels using molecular modeling and dynamics simulations. They show that isoform-specific glycosylation on Na_V1.5 and Na_V1.8 alters the binding sites of regulatory β-subunits, potentially contributing to β-subunit homo-oligomerization and Na_V channel supramolecular clustering.

In macroscopic electrophysiological experiments, the maximal probability of being active (P_A,max) is typically determined by comparing the response to a saturating concentration of the test agonist to the response to a reference agonist. Germann et al. present an approach to estimate P_A,max at subsaturating concentrations of test agonist.