Role of ATP sensitive K^+ channel in intracellular Ca^<2+> regulation.

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OBJECTIVE : We investigated the roles of ATP sensitive K^+ channel (K_<ATP>) and Na^+/Ca^<2+> exchanger in intracellular Ca^<2+> regulation.METHODS : Single enzymatically isolated guinea pig ventricular myocytes were exposed to chemical hypoxia with glucose-free Tyrode solution containing 1mM sodium dithionite and were reoxygenated. Intracellular Ca^<2+> concentration ([Ca^<2+>]i) was measured ratiometrically using fura-2 with simultaneous measurement of cell length. Isolated hearts from Sprague-Dawley rats were retrogradely perfused and [Ca^<2+>]i was monitored using fura-2. Ischemia was induced by reduction of flow to 10% of control with electrical pacing.RESULTS : Hypoxia produced a decrease in Ca^<2+> transient amplitude and an increase in resting [Ca^<2+>]i. K_<ATP> operner accelerated the shortening of action potential duration and suppressed the hypoxic increase in resting [Ca^<2+>]i. The increase in [Ca^<2+>]i induced by Na^+-free exposure was inhibited during hypoxia.Ischemia also produced an increase in diastolic [Ca^<2+>]i. Treatment of reverse mode Na^+/Ca^<2+> exchanger blocker attenuated the increase in diastolic [Ca^<2+>]i during sustained ischemia and accelerated normalization of [Ca^<2+>] i after reperfusion.CONCLUSIONS : Both K_<ATP> and Na^+/Ca^<2+> exchanger were importantly involved in intracellular Ca^<2+> regulation during ischemia and reperfusion.