Abstract

The possibility of physiologically-evoked muscarinic excitatory synaptic potentials was examined in the inferior mesenteric ganglion (IMG) with intracellular microelectrodes in vitro. Three types of depolarizing responses were evoked concurrently by colonic distension: (1) fast nicotinic excitatory postsynaptic potentials (EPSPs); (2) an ‘intermediate’ time course depolarization and (3) a long time course potential that persisted throughout the period of distension. After hexamethonium was superfused over the ganglia the long time course potential was observed in 91% of IMG neurons. Intermediate time course depolarizations were observed in 100% of IMG neurons and correlated with each propulsive contraction of the distal colon. The intermediate depolarizations had an average amplitude of 1.8 ± 0.1 mV ( n = 175 individual events; 27 preparations) with an average duration of 11.9 ± 0.8 sec ( n = 28 individual events). The intermediate time course synaptic potentials were accompanied by an increase in input resistance of 15% ( n = 6). Superfusion of atropine (1 μM; n = 6) on the IMG or the M 1-selective antagonist pirenzepine (1 μM; n = 5) abolished the intermediate time course synaptic potentials during distension. Superfusion of the M 2-selective antagonist AF-DX 116 (1 μM; n = 4) had no effect. In all preparations examined, distension-induced intermediate time course depolarizations were blocked by tetrodotoxin (TTX) (3 μM). Pressure ejection of carbachol (1 mM, 60–100 ms pulses) evoked depolarizations of similar amplitude (6.5 ± 0.7 mV; n = 18) and duration to the intermediate depolarizations observed during propulsive contractions. In all preparations examined, carbachol-induced depolarizations were antagonized by atropine (1 μM) and pirenzepine (1 μM) but not by AF-DX 116 (1 μM). These experiments demonstrate the existence of a physiologically-evoked muscarinic excitatory synaptic potential in IMG neurons of the guinea pig which is mediated through the M 1-receptor subtype.

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