OBJECTIVETo investigate the mechanism of ATP-sensitive potassium channel (K(ATP)) activator cromakalim (CRK) on action potentials and transient inward current (I(ti)) in isolated guinea pig papillary and ventricular myocytes and to explore the mechanisms of effects of I(ti) and K(ATP) treatment in idiopathic ventricular tachycardia.

METHODSThe whole-cell patch clamp recording technique was used to detect the action potentials and I(ti) and K(ATP) current alterations during the stimulated and triggered activity. Myocytes were isolated from guinea pig ventricle by enzyme digestion. The experiment was divided into four groups: (1) Control; (2) Control + Ouabain; (3) Control + CRK; (4) Control + Ouabain + CRK. (5) Control + Ouabain + CRK + glibenclamide (GLB). The action potential of guinea pig papillary muscles was measured by using standard microelectrode. The parameters in the experiment included the amplitude (APA), resting potentials (RP), action potentials duration (APD), as well as maximum rise of the action potential (Vmax).

RESULTS(1) When the guinea pig ventricular papillary myocytes were pretreated with Ouabain 0.5 micromol/L, APD prolonged significantly, especially APD(20), APD(50), APD(90). Delayed after depolorazion (DAD) and triggered activity were elicited. I(ti) currents and DAD as well as triggered activity increased. I(ti) current was (126.9 +/- 10.8) pA, lagT (1173.0 +/- 70.9) ms (n = 10, P < 0.01). (2) When guinea pig ventricular myocytes were pretreated with CRK (10 micromol/L), APD was shortened and the amplitude of DAD was lowered. The coupling time in CRK group was significantly prolonged compared with Ouabain group (n = 10, P < 0.01). (3) CRK 50 micromol/L pretreatment of the ventricular myocytes led to an increase of K(ATP) up to (342 +/- 89) pA, which was statistically significant as compared with the control group (P < 0.01). ATP-sensitive potassium channel blocker glibenclamide (10 micromol/L) could antagonize the effects of CRK on APD and I(ti) currents.

CONCLUSIONCRK might reduce the toxic effect of Ouabain on cardiomyocytes, shorten APD, terminate DAD and trigger excitation, and have protective effect on cardiomyocytes. The effects of CRK, may be associated with the inhibiting I(ti) current and increasing K(ATP).