POTENTIATING EFFECT OF ACETYLCHOLINE ON STIMULATION BY ISOPROTERENOL OF L-TYPE CA2-PIG VENTRICULAR MYOCYTES( CURRENT AND ARRHYTHMOGENIC TRIGGERED ACTIVITY IN GUINEA)

Introduction: The objective of this study was to determine whether the effect of isoproterenol (Iso) to increase L-type Ca2+ current [I-Ca(L )] and action potential duration (APD) was potentiated in ventricular myocytes following termination of an exposure of these cells to acetyl choline (ACh), and whether this potentiating effect of ACh could be ar rhgthmogenic. Methods and Results: Transmembrane currents and potentia ls of guinea pig isolated ventricular myocytes were measured using the whole cell, patch clamp technique. Stimulation of I-Ca(L) and prolong ation of APD caused by Iso (10 nmol/L) were attenuated in the presence of ACh (10 mu mol/L), but were transiently enhanced by 111% +/- 20% a nd 214% +/- 44%, respectively, following termination of a 2- to 4-minu te exposure of myocytes to ACh, No changes were observed in the absenc e of Iso, Both the amplitude and incidence of Iso-induced transient in ward current, afterdepolarizations, and sustained triggered activity w ere greater immediately after termination of exposure to ACh than befo re application of ACh, Conclusion: Stimulation by Iso of I-Ca(L) is tr ansiently enhanced in guinea pig ventricular myocytes following termin ation of exposure of these cells to ACh, The rebound increase of Iso-s timulated I-Ca(L) is associated with an increase of APD and induction of arrhythmogenic triggered activity.