Effect of acetylcholine on membrane currents in guinea-pig papillary muscle

1. The effect of acetylcholine (ACh) on the membrane current components in guinea-pig papillary muscle was studied by the single sucrose gap voltage clamp method. 2. The slow inward current (is) elicited by various depolarizations from the holding potential of -40 mV was evidently diminished by ACh greater than 5 x 10(-7) M. The amplitude of is, estimated as the difference between the peak of is and the current at 150 msec, was reduced to 56.8 +/- 12.9% (mean +/- S.D., n = 34) by 2 x 10(-8) M-ACh when estimated at the membrane potential where the amplitude was maximal. 3. is was suppressed almost completely by 2 mM-Co2+, is obtained by subtracting the current remaining in 2 mM-Co2+ was also diminished to the same extent by 2 x 10(-6) M-Ach with little change in its time course; the degree of decrease was not dependent on the membrane potential. 4. The time-dependent outward current during the depolarizing pulse was also diminished by 2 x 10(-6) M-Ach. Correspondingly, the positive tail current obtained when the membrane was repolarized to the holding potential of -40 mV after various 1 sec depolarizations was reduced in a proportionate manner to 68.6 +/- 7.3% (n = 10). 5. The time-independent inward rectifying outward current was not affected by 2 x 10(-6) M-Ach. 6. Atropine (10(-6) M) restored is and the time-dependent outward current which had been previously depressed by 2 x 10(-6) M-ACh. 7. ACh may decrease tension development by depressing is, thereby preserving the duration of the action potential with relatively little change, since, different from atrial muscle, ACh does not increase the outward current in mammalian ventricular muscle.