A non-adrenergic, non-cholinergic slow inhibitory post-synaptic potential in neurones of the guinea-pig submucous plexus.

1. Intracellular recordings were made from neurones in the submucous plexus of guinea-pig ileum and caecum. The responses to electrical stimulation of fibre strands entering the nodes of the plexus were studied. 2. Stimuli comprising trains of pulses (20 Hz, 1-5 s) produced nicotinic excitatory post-synaptic potentials (fast e.p.s.p.s), an adrenergic inhibitory post-synaptic potential (i.p.s.p.), a slow excitatory post-synaptic potential (slow e.p.s.p.) and a fourth, hitherto unnoticed, slow hyperpolarization which followed the slow e.p.s.p. All these responses were abolished by tetrodotoxin or solutions containing a low calcium concentration. 3. The slow hyperpolarization (slow i.p.s.p.) was examined in the presence of blockers of the nicotinic and adrenergic responses, and in conditions in which the slow e.p.s.p. was prevented by desensitizing concentrations of substance P or vasoactive intestinal polypeptide. The slow i.p.s.p. was unaffected by prazosin (0.1-1 microM), propranolol (0.1-1 microM), atropine (1 microM) or naloxone (1 microM). 4. The amplitude and duration of the slow i.p.s.p. increased with increasing numbers of stimulus pulses; it had an amplitude of 17 mV and a duration of 70 s when evoked by a stimulus of 20 Hz for 3 s. 5. The slow i.p.s.p. was associated with a decrease in the input resistance of the cell. It reversed polarity at -90 mV in 4.7 mM-potassium and the extrapolated reversal potential in 0.47 mM-potassium was -145 mV; these findings indicate that the slow i.p.s.p. results from an increase in membrane potassium conductance. 6. The slow i.p.s.p. could still be recorded from submucous plexus neurones in segments of ileum which had been extrinsically denervated 6-11 days previously.(ABSTRACT TRUNCATED AT 250 WORDS)