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

TLDR: Assessment of expression and remodeling of mechanosensitive K2P channels in atrial fibrillation (AF) and heart failure (HF) patients in comparison to murine models suggested a mechanistic contribution to cardiac arrhythmogenesis.

Abstract: Two-pore-domain potassium (K 2P ) channels modulate cellular excitability The significance of stretch-activated cardiac K 2P channels (K 2P 21, TREK-1, KCNK 2; K 2P 41, TRAAK, KCNK 4; K 2P 101, TREK-2, KCNK 10) in heart disease has not been elucidated in detail The aim of this work was to assess expression and remodeling of mechanosensitive K 2P channels in atrial fibrillation (AF) and heart failure (HF) patients in comparison to murine models Cardiac K 2P 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 KCNK 2 displayed highest mRNA abundance among mechanosensitive members of the K 2P channel family (V > A) Disease-associated K 2P 21 remodeling was studied in detail In patients with impaired left ventricular function, atrial KCNK 2 (K 2P 21) mRNA and protein expression was significantly reduced In AF subjects, downregulation of atrial and ventricular KCNK 2 (K 2P 21) mRNA and protein levels was observed AF-associated suppression of atrial Kcnk 2 (K 2P 21) mRNA and protein was recapitulated in CREM-transgenic mice Ventricular Kcnk 2 expression was not significantly altered in mouse models of disease In conclusion, mechanosensitive K 2P 21 and K 2P 101 K + channels are expressed throughout the heart HF- and AF-associated downregulation of KCNK 2 (K 2P 21) mRNA and protein levels suggest a mechanistic contribution to cardiac arrhythmogenesis