Sarco/Endoplasmic Reticulum Ca2+-ATPase is a more effective calcium remover than Sodium-Calcium Exchanger in human embryonic stem cell-derived cardiomyocytes.

Sarco/Endoplasmic Reticulum Ca2+-ATPase is a more effective calcium remover than Sodium-Calcium Exchanger in human embryonic stem cell-derived cardiomyocytes. Am J Physiol Heart Circ Physiol. 2019 Jul 26;: Authors: Li S, Chopra A, Keung W, Chan C, Costa KD, Kong CW, Hajjar RJ, Chen C, Li R Abstract Human pluripotent stem cell (hPSCs)-derived ventricular (V) cardiomyocytes (CMs) display immature Ca2+-handing properties with smaller transient amplitudes and slower kinetics due to such differences in crucial Ca2+-handling proteins as the poor sarco/endoplasmic reticulum Ca2+-ATPase (SERCA) pumpbut robust Na-Ca exchanger (NCX) activities in human embryonic stem cell (ESC)-derived VCMs compared to adult. Despite their fundamental importance in excitation-contraction coupling, the relative contribution of SERCA and NCX to Ca2+-handling of hPSC-VCMs remains unexplored.We systematically altered the activities of SERCA and NCX in hESC-VCMs and their engineered micro-tissues, followed by examining the resultant phenotypic consequences. SERCA overexpression in hESC-VCMs shortened the decay of Ca2+transient at low frequencies (0.5Hz) without affecting the amplitude, SR Ca2+content and Ca2+ baseline. Interestingly, shRNA-based NCX suppression did not prolong the transient decay, indicating a compensatory response for Ca2+removal. Although hESC-VCMs and their derived microtissues exhibited negative frequency-transient/force responses, SERCA overex...
Source: American Journal of Physiology. Heart and Circulatory Physiology - Category: Physiology Authors: Tags: Am J Physiol Heart Circ Physiol Source Type: research