Issues

JGP study reveals that the D-type K⁺ current regulates coincidence detection by shaping electrical transmission between pairs of MesV neurons.

This commentary focuses on a recently published article that featured manganese quench measurements in skeletal muscle, in particular a transient quench signal that was thought to represent Ca²⁺ transiently displacing Mn²⁺ bound to endogenous Ca²⁺ buffers inside muscle cells. The article explains these concepts in terms of the physical chemistry of calcium and manganese ligand binding.

Electrophysiological potentiation is calculated from the ratio of amplitudes of responses to agonist in the presence and absence of a modulator. Steinbach and Akk show that potentiation depends on the relative magnitude of the control response and provide equations to calculate the expected potentiating effect at different levels of control responses.

Practical advice to those who use permeabilized muscle preparations for mechanics experiments. This article covers the storage and preparation of samples, equipment considerations, and best practices to make experimental protocols reproducible.

Electrical synapses enable neural circuits to perform as coincidence detectors, that is, to preferentially respond to simultaneous inputs. The temporal precision of this operation is critically determined by voltage-dependent conductances of the soma and proximal axon.

Lopez-Mateos et al.’s study demonstrates AlphaFold2’s potential to sample multiple states of human NaV channels. Additionally, NaV α-subunit interactions with β-subunits and calmodulin reshape NaV α-subunit conformational landscape. This study reveals the potential of deep learning methods to model structural diversity of ion channels.

Sun et al. show that the commonly used Ca_V3 T-type channel-selective antagonists, ML218 and Z944, modulate the activity of Ca_V1.4 L-type channels through a mechanism involving the dihydropyridine-binding site.

Cell culture and molecular dynamics simulations reveal the role of claudin-15 D55 residue in ion size and charge selectivity. A reduced model of claudin-15 offers novel insights into ion conductance, providing a valuable tool for therapeutic modulation of tight junctions.

In cardiac pacemaker cells, AMPK activation by AMP in low-energy conditions reduces the I_f current and slows cardiac rate, an energy-saving mechanism. This work shows that AMPK inhibits HCN4 membrane expression by direct channel phosphorylation, and shows that this process contributes to age-dependent intrinsic rate slowing.

Using a prepulse protocol on insect Ca_V4 calcium channel, Cens et al. reported a current facilitation restricted to the descending branch of the I–V curve. Facilitation was less pronounced when the loop III–IV inactivation motif MFLT (homologous to the IFMT sequence on Na_V channels) was mutated. They propose a link between facilitation and inactivation.