Cell swelling causes the action potential duration to shorten in guinea-pig ventricular myocytes by activating IKATP

In guinea-pig ventricular myocytes, cell swelling by incubation in hypotonic solution caused a pronounced shortening of the action potential duration (APD(90): 15.5+/-14.6% compared to control; mean +/- SD) after a latency of 12 min when the intracellular ATP concentration was 2 mM, This shortening was partially reversible within 10 min after reperfusion with isotonic solution (APD(90),: 80.5+/-12.1% compared to control). With 5 mM intracellular ATP in the pipette electrode, the effect of cell swelling on the action potential was significantly reduced. Incubation with 1 mu M glibenclamide, a blocker of the ATP-dependent K+ current (I-KATP) abolished the swelling-induced shortening of the action potential duration, whereas incubation with 0.5 mM 4,4'-diisothiocyanatostilbene-2.2'-disulphonic acid (DIDS), a blocker of the swelling-induced Cl- current (I-Cl,I-swell), had no effect on the action potential duration in hypotonic solution. Simultaneous measurements of membrane currents substantiate that I-KATP is the current that underlies this effect. These results suggest that in the ischaemic myocardium I-KATP may be partially activated by cell swelling, resulting in a shortening of the action potential duration before the intracellular ATP concentration has fallen below 2 mM.