Muscarinic agonists inactivate potassium conductance of guinea-pig myenteric neurones.

1. The effects of muscarinic agonists applied both by perfusion and ionophoresis to myenteric neurones of the guinea-pig ileum were investigated by intracellular recording methods. 2. Perfusion with muscarinic agonists (acetylcholine, oxotremorine, methacholine, bethanechol) in concentrations of 100 nM to 10 microM caused membrane depolarizations. Brief ionophoretic applications of oxotremorine, or acetylcholine in the presence of hexamethonium, evoked depolarizations with a latency of 100 ms to 1 s and a duration of 5-60 s. 3. The depolarizations were completely antagonized by low concentrations (1-10 nM) of the muscarinic antagonists hyoscine or atropine. 4. The latency and time course of the muscarinic depolarizations were about one thousand times longer than those of nicotinic responses evoked in the same cell by acetylcholine applied from the same ionophoresis electrode. 5. The muscarinic depolarization was associated with a conductance decrease and reversed polarity at a membrane potential close to the potassium equilibrium potential. 6. The muscarinic depolarization became smaller but did not disappear completely during prolonged (up to 60 min) perfusion or repeated (more than 0.02 Hz) ionophoretic applications of muscarinic agonists. 7. Lower concentrations (3-30 nM) of oxotremorine, which did not change membrane potential, reduced the amplitude and duration of the calcium-dependent increase in potassium conductance which follows a burst of action potentials. 8. It is concluded that the muscarinic depolarization of myenteric neurones is due to potassium inactivation.