Human induced pluripotent stem cell–derived atrial cardiomyocytes recapitulate contribution of the slowly activating delayed rectifier currents I_Ks to repolarization in the human atrium

Human induced pluripotent stem cell–derived atrial cardiomyocytes (hiPSC-aCM) could be a helpful tool to study the physiology and diseases of the human atrium. To fulfil this expectation, the electrophysiology of hiPSC-aCM should closely resemble the situation in the human atrium. Data on the contribution of the slowly activating delayed rectifier currents (I_Ks) to repolarization are lacking for both human atrium and hiPSC-aCM.

Human atrial tissues were obtained from patients with sinus rhythm (SR) or atrial fibrillation (AF). Currents were measured in human atrial cardiomyocytes (aCM) and compared with hiPSC-aCM and used to model I_Ks contribution to action potential (AP) shape. Action potential was recorded by sharp microelectrodes. HMR-1556 (1 µM) was used to identify I_Ks and to estimate I_Ks contribution to repolarization. Less than 50% of hiPSC-aCM and aCM possessed I_Ks. Frequency of occurrence, current densities, activation/deactivation kinetics, and voltage dependency of I_Ks did not differ significantly between hiPSC-aCM and aCM, neither in SR nor AF. β-Adrenoceptor stimulation with isoprenaline did not increase I_Ks neither in aCM nor in hiPSC-aCM. In tissue from SR, block of I_Ks with HMR-1556 did not lengthen the action potential duration, even when repolarization reserve was reduced by block of the ultra-rapid repolarizing current with 4-aminopyridine or the rapidly activating delayed rectifier potassium outward current with E-4031.

I_Ks exists in hiPSC-aCM with biophysics not different from aCM. As in adult human atrium (SR and AF), I_Ks does not appear to relevantly contribute to repolarization in hiPSC-aCM.