HERG1 channel subunit composition mediates proton inhibition of rapid delayed rectifier potassium current (I_Kr) in cardiomyocytes derived from hiPSCs.

ABSTRACT: The voltage-gated channel, hERG1, conducts the rapid delayed rectifier potassium current (I_Kr) and is critical for human cardiac repolarization. Reduced I_Kr causes long QT syndrome and increases the risk for cardiac arrhythmia and sudden death. At least two subunits form functional hERG1 channels, hERG1a and hERG1b. Changes in hERG1a/1b abundance modulate I_Kr kinetics, magnitude, and drug sensitivity. Studies from native cardiac tissue suggest that hERG1 subunit abundance is dynamically regulated, but the impact of altered subunit abundance on I_Kr and its response to external stressors is not well understood. Here, we used a substrate-driven human-induced pluripotent stem cell-derived cardiomyocyte (hiPSC-CM) maturation model to investigate how c

SUBMITTER: Ukachukwu CU 

PROVIDER: S-EPMC9867984 | biostudies-literature | 2023 Feb

REPOSITORIES: biostudies-literature