TASK-1 and TASK-3 Channels Modulate Pressure Overload Induced Cardiac Remodeling and Dysfunction.

TASK-1 and TASK-3 Channels Modulate Pressure Overload Induced Cardiac Remodeling and Dysfunction. Am J Physiol Heart Circ Physiol. 2020 Jan 24;: Authors: Duan W, Hicks J, Makara MA, Ilkayeva OR, Abraham DM Abstract Tandem pore domain acid sensitive K+ (TASK) channels are present in cardiac tissue, however their contribution to cardiac pathophysiology is not well understood. Here, we investigate the role of TASK-1 and TASK-3 in the pathogenesis of cardiac dysfunction using both human tissue and mouse models of genetic TASK channel loss of function. In comparison to normal human cardiac tissue, TASK-1 gene expression is reduced in association with either cardiac hypertrophy alone or combined cardiac hypertrophy and heart failure. In a pressure overload cardiomyopathy model, TASK-1 global knockout (TASK-1 KO) mice have both reduced cardiac hypertrophy and preserved cardiac function in comparison to Wild Type mice. In contrast to the TASK-1 KO mouse pressure overload response, TASK-3 global knockout (TASK-3 KO) mice develop cardiac hypertrophy and a delayed onset of cardiac dysfunction in comparison to Wild Type mice. The cardioprotective effects observed in TASK-1 KO mice are associated with pressure overload induced augmentation of AKT phosphorylation and PGC-1 alpha, improved cardiac energetics and fatty acid oxidation. The protective effects of TASK-1 loss of function are associated with an enhancement of physiologic hypertrophic sig...
Source: American Journal of Physiology. Heart and Circulatory Physiology - Category: Physiology Authors: Tags: Am J Physiol Heart Circ Physiol Source Type: research