Ion channel signalling articles from across Nature Portfolio

The molecular basis of OSCA/TMEM63 channel mechanosensitivity was investigated by determining 44 cryogenic electron microscopy structures of channels in different environments, expanding understanding of channel-mediated mechanotransduction and pore formation, with implications for two protein families.

Human pluripotent stem cells have been shown to be important models for interrogating the molecular basis for heart disease. This review highlights the contributions of these models to our understanding of inherited arrhythmia syndromes, with a focus on integrating mechanistic and genome-wide association study data.

Romero-Becerra et al. report that stress kinases p38γ and p38δ are activated in ventricles of old mice and in arrhythmogenic conditions, and they demonstrate that p38γ/δ -driven phosphorylation of RyR2 and SAP97 is a trigger for ventricular fibrillation.

Ventricular arrhythmias are associated with aging and are a leading cause of sudden cardiac death. A new study shows that hyperactivation of p38γ/δ MAPKs is a key driver of stress-induced ventricular arrhythmias via increased phosphorylation of ryanodine receptor 2 at Ser2367 and impaired localization of potassium voltage-gated channel K_v4.3.

Global or macrophage-specific knockout of Trpm2, which encodes the calcium-permeable ion channel TRPM2, protects mice against atherosclerosis induced by a high-fat diet. Mechanistically, activation of TRPM2 and the scavenger receptor CD36 promote the transformation of macrophages into inflammatory foam cells, thereby accelerating the development and progression of atherosclerosis.