CARDIOTOXICITY OF EMETINE DIHYDROCHLORIDE BY CALCIUM-CHANNEL BLOCKADEIN ISOLATED PREPARATIONS AND VENTRICULAR MYOCYTES OF GUINEA-PIG HEARTS

1 The cardiotoxic effects of emetine dihydrochloride on mechanical and electrical activity were studied in isolated preparations (papillary muscles, sinoatrial and atrioventricular nodes, ventricular myocytes) of the guinea-pig heart.2 Force of contraction was measured isometrica lly, action potentials and maximum rate of rise of the action potentia l were recorded by means of the intracellular microelectrode technique . Single channel L-type calcium current (Ba2+ ions as charge carrier) was studied with the patch-clamp technique in the cell-attached mode. 3 Emetine dihydrochloride (8-256 mu M) reduced force of contraction in papillary muscles and spontaneous activity of sinoatrial and atrioven tricular nodes concentration-dependently; the negative inotropic effec t was abolished when the extracellular Ca2+ concentration was increase d. 4 Maximum diastolic potential, action potential amplitude, maximum rate of rise of the action potential and the slope of the slow diastol ic depolarization were decreased by emetine in sinoatrial as well as a trioventricular nodes, while action potential duration was prolonged i n both preparations (1-64 mu M). 5 The amplitude of the L-type calcium single channel current was not altered by emetine dihydrochloride, wh ile average open state probability was decreased concentration-depende ntly (10, 30 and 60 mu M). 6 The most prominent effect of emetine dihy drochloride on single channel current was an increase of sweeps withou t activity. 7 At 60 mu M, emetine dihydrochloride caused a decrease of the mean open time and an increase of the mean closed time. The numbe r of openings per record and number of bursts per record were reduced. 8 It is concluded that emetine dihydrochloride produces an L-type cal cium channel block which might contribute to its cardiac side effects.