Dual mechanism for inhibition of calcium-dependent action potentials by acetylcholine in avian ventricular muscle. Relationship to cyclic AMP.

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Abstract
Acetylcholine (ACh) and carbamylcholine (Carb) inhibited Ca-dependent action potentials and contractions in ventricular muscle from the avian heart. The inhibition by cholinergic drugs was antagonized by atropine (muscarinic) and occurred by 2 pathways, indirect and direct. Before hatching, ACh had no effect but it inhibited Ca-dependent action potentials that were augmented by isoproterenol (ISO). This indirect pathway for inhibition was detected as early as the 7th incubation day. Acetylcholine had no effect on basal cyclic[c]AMP content, but it reduced cAMP when the nucleotide was increased by ISO. After hatching, ACh inhibited Ca-dependent action potentials and contractions indirectly and directly. Direct inhibition by ACh occurred in preparations treated with 6-hydroxydopamine (or reserpine) and propranolol, so that endogenous cardiac catecholamines probably were not involved. Basal levels of cAMP increased after hatching and direct inhibition by ACh was associated with a reduction of cAMP. These results are interpreted in a model in which cAMP modulates the permeability of the membrane to Ca2+ and in which GTP regulates the .beta.-adrenergic receptor and adenylate cyclase. The indirect muscarinic inhibition may be due to interference with GTP-dependent regulation of .beta.-adrenergic receptor/adenylate cyclase interaction and direct muscarinic inhibition may result from interference with GTP-dependent regulation of adenylate cyclase.

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