The time course of muscarinic depolarization of guinea-pig myenteric neurones.

Intracellular recordings were made from neurones in the myenteric plexus of the guinea-pig ileum in vitro. Muscarinic depolarizations were evoked by brief (1-500 ms) ionophoretic applications of acetylcholine (ACh) or other agonists. Nicotinic responses to ACh evoked by the same ionophoretic pulse had short latencies and rapid rise times, indicating close proximity of the ionophoretic pipette to the neurone membrane. The time course (duration several seconds) of the muscarinic depolarization was independent of the identity of the agonists applied (ACh, methacholine, carbachol, oxotremorine). Hyoscine and barium were ejected onto the neurones by brief (30 ms-1 s) pressure pulses applied to micropipettes. Hyoscine applied immediately after ACh, during the latency and rising phase of the muscarinic depolarization, did not antagonize the response to ACh. The same application of hyoscine immediately prior to ACh caused complete antagonism. Muscarinic depolarizations evoked by continuous application of ACh (by repeated ionophoresis or perfusion) were reversed by hyoscine. The time course of this reversal was similar to the decline of the muscarinic response following a single brief application of ACh. Barium caused a depolarization similar to that produced by muscarinic agonists in its latency, time course and temperature sensitivity, and having the same reversal potential (-90 mV). These barium potentials were not affected by hyoscine. It is suggested that neither diffusion of ACh to the receptors nor the kinetics of the agonist-receptor interaction contributes significantly to the latency and prolonged time course of the muscarinic depolarization.