Regulation of Ca2+ signaling by acute hypoxia and acidosis in cardiomyocytes derived from human induced pluripotent stem cells

•Human Induced Pluripotent Stem Cell–derived CMs express two cell populations based on inactivation kinetics of L-type ICa (τi 20ms & 50ms).•The diverse expression of slowly and rapidly inactivating ICa in hiPSC-CMs is responsible for variability in action potential morphology.•Suppressive effects of hypoxia were larger in slowly vs rapidly inactivating ICa, suggesting CDI protects the channels against hypoxia.•The varied inhibition of ICa in both cell types disappeared when Ba2+ was the charge carrier, suggesting critical role for CDI in hypoxic response.•Inhibition of focal Ca2+ transients by hypoxia or acidosis was more consistent with suppressive effects of these interventions on SR Ca2+ content. The effects of acute (100 s) hypoxia and/or acidosis on Ca2+ signaling parameters of human induced pluripotent stem cell-derived cardiomyocytes (hiPSC-CM) are explored here for the first time. 1) hiPSC-CMs express two cell populations: rapidly-inactivating ICa myocytes (τi