Piezo1 and BK
Adult
Aged
Aged, 80 and over
Arrhythmia, Sinus
/ metabolism
Atrial Fibrillation
/ metabolism
Atrial Remodeling
/ drug effects
Calcium
/ metabolism
Cells, Cultured
Female
Gene Knockdown Techniques
Heart Atria
/ metabolism
Humans
Indoles
/ pharmacology
Ion Channels
/ genetics
Ion Transport
/ drug effects
Large-Conductance Calcium-Activated Potassium Channel alpha Subunits
/ agonists
Male
Middle Aged
Myofibroblasts
/ metabolism
Peptides
/ pharmacology
Signal Transduction
/ drug effects
Tetrazoles
/ pharmacology
Thiourea
/ analogs & derivatives
Transfection
Arrhythmia
Calcium
Heart
KCNMA1
Mechano-sensing
Non-myocytes
Stretch-activated ion channels
Journal
Journal of molecular and cellular cardiology
ISSN: 1095-8584
Titre abrégé: J Mol Cell Cardiol
Pays: England
ID NLM: 0262322
Informations de publication
Date de publication:
09 2021
09 2021
Historique:
received:
14
05
2020
revised:
18
04
2021
accepted:
04
05
2021
pubmed:
12
5
2021
medline:
29
1
2022
entrez:
11
5
2021
Statut:
ppublish
Résumé
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
Identifiants
pubmed: 33974928
pii: S0022-2828(21)00096-1
doi: 10.1016/j.yjmcc.2021.05.002
pii:
doi:
Substances chimiques
1-(3,5-bis(trifluoromethyl)phenyl)-3-(4-bromo-2-(1H-tetrazol-5-yl)phenyl)thiourea
0
Indoles
0
Ion Channels
0
KCNMA1 protein, human
0
Large-Conductance Calcium-Activated Potassium Channel alpha Subunits
0
PIEZO1 protein, human
0
Peptides
0
Tetrazoles
0
paxilline
3T9U9Z96L7
iberiotoxin
773HER9B6T
Thiourea
GYV9AM2QAG
Calcium
SY7Q814VUP
Types de publication
Journal Article
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
49-62Informations de copyright
Copyright © 2021. Published by Elsevier Ltd.