Acetylcholine increases resting membrane potassium conductance in atrial but not in ventricular muscle during muscarinic inhibition of Ca++-dependent action potentials in chick heart.

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Abstract
In atrial and ventricular cells from hearts of hatched chicks, acetylcholine reduced the overshoot and the duration of action potentials recorded in normal Tyrode''s solution (5.4 mM K+). This effect of acetylcholine is attributed to inhibition of the slow inward current-dependent portion of the action potential because acetylcholine reduced the overshoot, rate of rise, and duration of the Ca2+/Na+-dependent action potential recorded in 25 mM K+-Tyrode''s solution. Depolarization of the membrane to about -40 mV by 25 mM K+ inactivates the early inward Na+ current but not the slow inward current-dependent component of the action potential. Inhibition by acetylcholine, which requires occupation of muscarinic receptors, occurs in the absence of catecholamines and is designated as direct. Muscarinic inhibition of atrial cells is associated with membrane hyperpolarization and a reduction of membrane resistance. In contrast, muscarinic inhibition of ventricular cells occurs without hyperpolarization or a change of membrane resistance. Apparently, activation of atrial muscarinic receptors inhibits the slow inward current-dependent action potential by increasing outward background K+ current, and decreasing an inward Ca2+/Na+ current. In the ventricle, muscarinic inhibition is probably achieved by decreasing an inward Ca2+/Na+ current, alone. Inhibition by acetylcholine in ventricles is also distinguished by an interaction between muscarinic receptors and Ca2+ entry that appears to be noncompetitive, a result previously described in amphibian ventricles. In contrast, inhibition of mammalian atria by acetylcholine is characterized by competitive interaction between muscarinic receptors and Ca2+ influx. The results are consistent with the previously published model for the transition from indirect (antiadrenergic) to direct muscarinic inhibition observed after hatching. Evidently, the transition from direct to indirect muscarinic inhibition is not due to a change in the membrane conductance activated by acetylcholine in ventricular cells, but rather to a change in the regulation of adenylate cyclase activity by the parasympathetic neurotransmitter.