Anoxia-induced activation of ATP-sensitive Kq channels in guinea pig ventricular cells and its modulation by glycolysis

q.Objective: Exposure to anoxia has been reported to activate ATP-sensitive potassium K channels in isolated ventricularATP myocytes. We aimed to investigate the mechanisms underlying the anoxia-induced activation of Kq channels. Methods: Guinea pigATP ventricular myocytes were isolated using collagenase digestion. Action potentials and membrane currents were recorded in the whole-cell mode of patch clamp. Exposure to anoxia was performed in a semi-closed airtight chamber, which prevented the diffusion of atmospheric .oxygen into anoxic perfusate. Results: Exposure to glucose-free anoxia shortened the action potential duration APD to less than 20 % of control in 13"3 min. Subsequent reoxygenation rapidly and completely restored the APD. The time-independent large outward current which developed during anoxia was completely suppressed by reoxygenation or by the application of glibenclamide, a Kq channelATP blocker. The presence of extracellular glucose did not prevent APD shortening during anoxia, although it significantly decreased the rate of shortening. Reoxygenation-induced restoration of the APD was inhibited after a long-lasting anoxia. In addition, repeated exposures to anoxiarreoxygenation progressively impaired the recovery of APD during reoxygenation. Conclusions: Activation of Kq channelsATP occurs during anoxia. The primary source of ATP that regulates the channel activity seems to be oxidative phosphorylation. ATP derived .from anaerobic glycolysis attained by the increase of extracellular glucose was observed to partially suppress the channel activity onl