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

Aims 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. Methods and results 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. Conclusion 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. [ABSTRACT FROM AUTHOR]