In guinea-pig ventricular myocytes, cell swelling by incubation in hypotonic solution caused a pronounced shortening of the action potential duration (APD90: 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 (APD90: 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 microM glibenclamide, a blocker of the ATP-dependent K+ current (IKATP), 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 (ICl,swell), had no effect on the action potential duration in hypotonic solution. Simultaneous measurements of membrane currents substantiate that IKATP is the current that underlies this effect. These results suggest that in the ischaemic myocardium IKATP 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.