HCN4 and Arrhythmias: Insights into Base Mutations

Mutation Research/Reviews in Mutation Research, Journal Year: 2025, Volume and Issue: 795, P. 108534 - 108534

Published: Jan. 1, 2025

Language: Английский

Structure mirroring function: What's the ‘matter’ with the funny current?

The Journal of Physiology, Journal Year: 2025, Volume and Issue: unknown

Published: Feb. 27, 2025

Abstract First described in native cardiac pacemaker cells, the ‘funny’ ( I f ) current provided a novel mechanism able to underlie rhythmic activity and autonomic control of heart rate. Increasing impact this finding, new replaced previous pacemaking model based on ‘fake’ K + K2 ), shown fact be ‘camouflaged’ ; also, similar neurons h was found regulate neuronal excitability. , first inward activated hyperpolarization, had several other peculiar features, when investigated sinoatrial node tissue isolated cells. It mixed Na /K permeability, lowest patch clamp recorded single‐channel conductance, dually by voltage intracellular cyclic nucleotides. activation internal cAMP, property key modulation rate, involve direct cAMP binding channels. Finally, an blocking drug, ivabradine, suitable for pharmacological rate therapies against angina failure. Later cloning HCN channels, comprising subunit components funny allowed molecular insight into properties carried HCN4. Recently, cryogenic electron microscopy has resolved details HCN4 structure with unprecedented precision, providing way validate or refute, structural basis, original interpretation/modelling experimental data. This review aims compare elementary functional vs . protein structure. Does ‘mirror’ function? We show that characteristics originally are elegantly explained ‘mirrored’ features channel protein. image

Language: Английский

HCN4 in the atrioventricular node

Heart Rhythm, Journal Year: 2025, Volume and Issue: unknown

Published: Feb. 1, 2025

Language: Английский