Abstract

Acetylcholine (ACh) arrested pacemaker activity in isolated embryonic chick hearts at all stages examined during development (44 hours-21 days). This effect of ACh was blocked completely by atropine. Cardioinhibition by ACh was associated with membrane hyperpolarization and a reduced diastolic depolarization rate in pacemaker cells from embryos six days and older. In addition, ACh reduced action potential duration in atrial and sinus venosus (pacemaker) cells. These effects of ACh on the innervated embryonic heart, like those described in adult vertebrate hearts, were referable to an increased membrane conductance to K⁺ (g_K). In noninnervated (three- and four-day) embryonic hearts, cardioinhibition by ACh was accompanied by a decreased diastolic depolarization rate. In contrast to the findings in innervated hearts, membrane depolarization occurred and action potential duration was unchanged. Depolarization of noninnervated hearts by ACh depended upon an increase in g_Na for the depolarization was abolished in the absence of Na⁺. Moreover, ACh hyperpolarized in the absence of Na⁺ because the drug increased g_K as well as g_Na in noninnervated hearts. Improvement in the K electrode properties during development also contributed to determining the effects of ACh on membrane potentials. For example, the reduction in action potential duration by ACh became greater with developmental age. The results of this study are consistent with the hypothesis that changes in membrane conductance properties during development are responsible for the alterations observed in the actions of ACh on membrane potentials.