Kir2.1 and K2P1 channels reconstitute two levels of resting membrane potential in cardiomyocytes.

Outward and inward background currents across the cell membrane balance, determining resting membrane potential. Inward rectifier K+ channel subfamily 2 (Kir2) channels primarily maintain the resting membrane potential of cardiomyocytes. Human cardiomyocytes exhibit two levels of resting membrane potential at subphysiological extracellular K+ concentrations or pathological hypokalaemia, however, the underlying mechanism is unclear. In the present study, we show that human cardiomyocytes derived from induced pluripotent stem cells with enhanced expression of isoform 1 of Kir2 (Kir2.1) channels and mouse HL-1 cardiomyocytes with ectopic expression of two pore-domain K+ channel isoform 1 (K2P1) recapitulate two levels of resting membrane potential, indicating the contributions of Kir2.1 and K2P1 channels to the phenomenon. In Chinese hamster ovary cells that express the channels, Kir2.1 currents non-linearly counterbalance hypokalaemia-induced K2P1 leak cation currents, reconstituting two levels of resting membrane potential. These findings support the hypothesis that Kir2 currents non-linearly counterbalance inward background cation currents, such as K2P1 currents, accounting for two levels of resting membrane potential in human cardiomyocytes and demonstrating a novel mechanism that regulates excitability.

Pubmed ID: 28543529 RIS Download