Anoxia-induced activation of ATP-sensitive K+ channels in guinea pig ventricular cells and its modulation by glycolysis.
OBJECTIVE
Exposure to anoxia has been reported to activate ATP-sensitive potassium (K+(ATP)) channels in isolated ventricular myocytes. We aimed to investigate the mechanisms underlying the anoxia-induced activation of K+(ATP) channels.


METHODS
Guinea pig 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 K+(ATP) channel 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 anoxia/reoxygenation progressively impaired the recovery of APD during reoxygenation.


CONCLUSIONS
Activation of K+(ATP) channels 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 only when oxidative phosphorylation was severely impaired during anoxia.
Shigematsu
S
S
Department of Physiology, Oita Medical University, Japan.
Arita
M
M
D000200:Action Potentials; D000255:Adenosine Triphosphate / Q000378:metabolism*; D000818:Animals; D005905:Glyburide / Q000494:pharmacology; D006019:Glycolysis; D006168:Guinea Pigs; D000860:Hypoxia / Q000378:metabolism*; D015640:Ion Channel Gating; D009206:Myocardium / Q000378:metabolism*; D010085:Oxidative Phosphorylation; D018408:Patch-Clamp Techniques; D026902:Potassium Channel Blockers; D015221:Potassium Channels / Q000378:metabolism*
D026902:Potassium Channel Blockers; D015221:Potassium Channels; D000255:Adenosine Triphosphate; D005905:Glyburide