Stretch-activated two-pore-domain (K2P ) potassium channels in the heart: Focus on atrial fibrillation and heart failure

Progress in Biophysics and Molecular Biology
Constanze SchmidtDierk Thomas

Abstract

Two-pore-domain potassium (K2P) channels modulate cellular excitability. The significance of stretch-activated cardiac K2P channels (K2P2.1, TREK-1, KCNK2; K2P4.1, TRAAK, KCNK4; K2P10.1, TREK-2, KCNK10) in heart disease has not been elucidated in detail. The aim of this work was to assess expression and remodeling of mechanosensitive K2P channels in atrial fibrillation (AF) and heart failure (HF) patients in comparison to murine models. Cardiac K2P channel levels were quantified in atrial (A) and ventricular (V) tissue obtained from patients undergoing open heart surgery. In addition, control mice and mouse models of AF (cAMP-response element modulator (CREM)-IbΔC-X transgenic animals) or HF (cardiac dysfunction induced by transverse aortic constriction, TAC) were employed. Human and murine KCNK2 displayed highest mRNA abundance among mechanosensitive members of the K2P channel family (V > A). Disease-associated K2P2.1 remodeling was studied in detail. In patients with impaired left ventricular function, atrial KCNK2 (K2P2.1) mRNA and protein expression was significantly reduced. In AF subjects, downregulation of atrial and ventricular KCNK2 (K2P2.1) mRNA and protein levels was observed. AF-associated suppression of atrial Kcnk...Continue Reading

Citations

Aug 29, 2018·The Journal of Clinical Investigation·Dennis M AbrahamHoward A Rockman
Jun 21, 2018·Pharmacological Reviews·David CalvoJosé Jalife
Apr 1, 2020·Cardiovascular Research·Lia CrottiMichael C Sanguinetti
Jul 21, 2017·Channels·Ehsan Nematian-ArdestaniStephen J Tucker
Jul 19, 2018·Biophysics Reviews·Ann-Kathrin RahmDierk Thomas
Apr 10, 2019·Neural Regeneration Research·J Antonio Lamas, Diego Fernández-Fernández
Oct 23, 2019·International Journal of Molecular Sciences·Felix WiedmannConstanze Schmidt
May 28, 2019·Chemical Biology & Drug Design·Daniel Şterbuleac
Sep 2, 2020·International Journal of Molecular Sciences·Ramón CoboJose A Vega
Dec 16, 2020·Scientific Reports·Tatiana ZyrianovaAndreas Schwingshackl
Jun 20, 2020·Progress in Biophysics and Molecular Biology·Felix WiedmannConstanze Schmidt
May 6, 2021·Journal of Cardiovascular Development and Disease·Drew NassalThomas J Hund
May 19, 2021·Pflügers Archiv : European journal of physiology·Wenli DaiChristopher R Weber
Aug 28, 2021·International Journal of Molecular Sciences·Miklós LengyelGábor Czirják

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