thiourea and Atrial-Remodeling

Atrial Fibrillation (AF) is an arrhythmia of increasing prevalence in the aging populations of developed countries. One of the important indicators of AF is sustained atrial dilatation, highlighting the importance of mechanical overload in the pathophysiology of AF. The mechanisms by which atrial cells, including fibroblasts, sense and react to changing mechanical forces, are not fully elucidated. Here, we characterise stretch-activated ion channels (SAC) in human atrial fibroblasts and changes in SAC- presence and activity associated with AF.. Using primary cultures of human atrial fibroblasts, isolated from patients in sinus rhythm or sustained AF, we combine electrophysiological, molecular and pharmacological tools to identify SAC. Two electrophysiological SAC- signatures were detected, indicative of cation-nonselective and potassium-selective channels. Using siRNA-mediated knockdown, we identified the cation-nonselective SAC as Piezo1. Biophysical properties of the potassium-selective channel, its sensitivity to calcium, paxilline or iberiotoxin (blockers), and NS11021 (activator), indicated presence of calcium-dependent 'big potassium channels' (BK. Human atrial fibroblasts contain at least two types of ion channels that are activated during stretch: Piezo1 and BK

Topics: Adult; Aged; Aged, 80 and over; Arrhythmia, Sinus; Atrial Fibrillation; Atrial Remodeling; Calcium; Cells, Cultured; Female; Gene Knockdown Techniques; Heart Atria; Humans; Indoles; Ion Channels; Ion Transport; Large-Conductance Calcium-Activated Potassium Channel alpha Subunits; Male; Middle Aged; Myofibroblasts; Peptides; Signal Transduction; Tetrazoles; Thiourea; Transfection