A direct negative inotropic effect of acetylcholine on rat ventricular myocytes

Acetylcholine (ACh) decreased the contraction of rat ventricular cells within 20 s. ACh (3.1 x 10(-8) M) produced a half-maximal effect and 10(-6) M ACh produced a maximal effect (a 23.8 +/- 5.4% decrease; mean +/- SE, n = 11). During a 3-min exposure to ACh, the inotropic effect faded. Parallel changes were observed in action potential duration: ACh caused an immediate shortening of the action potential, but then the effect faded with time. The changes in action potential duration were the cause of the changes in contraction, because ACh had no effect on contraction when the contractions were triggered by voltage-clamp pulses of constant duration. The changes in action potential duration were the result of the activation of a K+ current (iK,ACh) by ACh. During an exposure to ACh, this current faded as a result of desensitization. iK,ACh was 6.3 times smaller in ventricular than in atrial cells. This may explain why the negative inotropic effect of ACh on atrial cells was greater: 1.0 x 10(-8) M ACh produced a half-maximal effect on atrial cells, and 10(-6) M ACh produced a near maximal effect (a 74.5 +/- 9.5% decrease; n = 4).