Issues

JGP study reveals how the neurotransmitter PACAP induces a secretory response in chromaffin cells that differs from the one induced by acetylcholine.

Inwardly rectifier potassium (Kir) channels are a major potassium channel sub-class whose function is regulated by ligand-dependent gating and highly voltage-dependent block by polyamines. With molecular dynamics simulations over previously unattainable timescales, Jogini et al. provide unprecedented visualization of K⁺ conduction through open Kir2.2 channels and of the molecular details of channel block by spermine.

Obliterating skeletal muscle Orai1 expression improves muscle pathology in the mdx mouse model of DMD—could Orai1 emerge as a potential drug target?

This Review discusses ion channel expression and function in immune cells, residential non-immune cells and neuroimmune interactions in the gut, and how ion channels contribute to the maintenance of intestinal immune homeostasis and generation of autoimmune disorders under pathological conditions.

Kiriaev et al. discuss how preparations, protocols, and factors impact sensitivity to ECC of dystrophin-deficient skeletal muscle.

Based on the results of long-timescale molecular dynamics simulations, Jogini et al. provide atomic-level mechanistic and structural descriptions of lipid-dependent gating and spermine-induced inward rectification of the inward-rectifier potassium channel Kir2.2.

The muscle regulatory protein tropomyosin relocates on thin filaments as the myosin motor binds to and releases from actin. We show that amino acid side chains at the tip of the myosin motor are critical for optimal tropomyosin repositioning.

We demonstrate that ASIC1a activates intermediate- and small-conductance Ca²⁺-activated K⁺ channels, which are essential mediators of endothelium-dependent hyperpolarization and vasodilation in mesenteric resistance arteries. Collectively, these data provide novel evidence that ASIC1a is an important contributor to endothelium-dependent vasodilation.

PACAP is an important neurotransmitter at the splanchnic-chromaffin cell synapse, but the mechanisms by which it stimulates secretion are poorly understood. Here we show that PACAP operates through a pathway that involves Gαs, PLCε, and L-type calcium channels.

We propose a new conformational cycle for NavAb wherein an α- to π-helix transition in S6 and disordering of the neck region of the C-terminal domain is important for pore opening.

Jeong et al. reveal that n-alcohols differentially regulate Kv7.2/7.3 channels depending on their carbon chain length. The findings suggest that long-chain n-alcohols regulate Kv7.2/7.3 channels through two separate binding sites and that their net stimulatory effects are associated with their anesthetic activity.