Two pore potassium channels (K2p) have been described in modulating background conductance as leak channels in different physiological systems. In the heart, the expression of K2p channels is heterogeneous with equivocation regarding their functional role. Our objective was to determine the K2p expression profile and their physiological and pathophysiological contribution to cardiac electrophysiology. Induced pluripotent stem cells (iPSC) cells generated from humans were differentiated into cardiomyocytes (iPSC-CM). mRNA was isolated from these cells, commercial iPSC-CM (iCells®), control human heart ventricular tissue (cHVT), ischemic (iHF) and non-ischemic heart failure tissues (niHF). We detected ten K2p in the heart. Comparing qPCR expression of K2p between human heart tissue and iPSC-CM revealed K2p1.1, K2p2.1, K2p5.1, and K2p17.1 to be higher expressed in cHVT whereas K2p3.1 and K2p13.1 were higher in iPSC-CM. Notably, K2p17.1 was significantly lower in niHF tissues compared to cHVT. Action potential recordings in iCells® following K2p siRNA knockdown revealed prolongations in APD90 for K2p2.1, K2p3.1, K2p6.1, K2p17.1. Here we report the expression level of ten human K2p channels in iPSC-CM and how they compare to cHVT. Importantly, our functional electrophysiological data in human iPSC-CM revealed a prominent role in cardiac ventricular repolarization for four of these channels. Finally, we also identified K2p17.1 as significantly reduced in niHF tissues and K2p4.1 as reduced in niHF compared to iHF. Thus, we advance the notion that K2p channels are emerging as novel players in cardiac ventricular electrophysiology that could also be remodeled in cardiac pathology and therefore contribute to arrhythmias.
- Two pore potassium channels
- induced pluripotent stem cell derived cardiomyocytes
- cardiac repolarization
- action potential duration
- heart failure
- Copyright © 2017, American Journal of Physiology-Heart and Circulatory Physiology