A kinetic model for the muscarinic action of acetylcholine

The timecourse of the membrane hyperpolarization evoked by stimulation of postganglionic parasympathetic nerve endings in isolated atria from the guinea-pig heart is mainly governed by two exponentials, one describing most of the rising phase (rate constant k alpha = 2.88+/-1.135 s-1) and one which completely describes the decline of the response (k beta = 0.58+/-0.31 s-1). An exact description of the muscarinic receptor mediated potential change, which also allows for its apparent latency and its s-shaped beginning, is found if two additional faster exponentials are introduced. In agreement with earlier results a model of four consecutive reactions is presented. It is concluded that during muscarinic cholinergic transmission reactions subsequent to binding of the ACh-molecules to the receptor are rate-limiting.