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Abstract: Background: Prevailing data suggest that ATP-sensitive potassium channels (KATP) contribute to a surprising resistance to hypoxia in mammalian embryos, thus we aimed to characterize the developmental changes of KATP channels in murine fetal ventricular cardiomyocytes. Methods: Patch clamp was applied to investigate the functions of KATP. RT-PCR, Western blot were used to further characterize the molecular properties of KATP channels. Results: Similar KATP current density was detected in ventricular cardiomyocytes of late development stage (LDS) and early development stage (EDS). Molecular–biological study revealed the upregulation of Kir6.1/SUR2A in membrane and Kir6.2 remained constant during development. Kir6.1, Kir6.2, and SUR1 were detectable in the mitochondria without marked difference between EDS and LDS. Acute hypoxia–ischemia led to cessation of APs in 62.5% of tested EDS cells and no APs cessation was observed in LDS cells. SarcKATP blocker glibenclamide rescued 47% of EDS cells but converted 42.8% of LDS cells to APs cessations under hypoxia-ischemic condition. MitoKATP blocker 5-HD did not significantly influence the response to acute hypoxia–ischemia at either EDS or LDS. In summary, sarcKATP played distinct functional roles under acute hypoxia-ischemic condition in EDS and LDS fetal ventricular cardiomyocytes, with developmental changes in sarcKATP subunits. MitoKATP were not significantly involved in the response of fetal cardiomyocytes to acute hypoxia–ischemia and no developmental changes of KATP subunits were found in mitochondria. [Copyright &y& Elsevier]