PRESYNAPTIC MUSCARINIC INHIBITION IN BULLFROG SYMPATHETIC-GANGLIA

1. Muscarinic modulation of nicotinic transmission was studied in bull frog sympathetic ganglia by recording synaptic currents from B and C n eurones. 2. Bath-applied muscarine reduced the amplitude of EPSCs reco rded at < 0.2 Hz from B neurones by up to 57%. The action was reversib le, showed no apparent desensitization, and had an EC(50) of 102 nM. M uscarine had no effect on EPSCs in C neurones. 3. Currents evoked by i onophoretic application of ACh to B neurones were unchanged by muscari ne, Muscarine increased the coefficient of variation (c.v.) of EPSC am plitude. The effect upon the ratio of c.v.(2)(control) to c.v.(2)(musc arine) was Proportional to the change in mean EPSC amplitude. 4. Activ ation of muscarinic receptors by ACh from nerve terminals was observed by comparing trains of EPSCs in normal Ringer solution and atropine. Inhibition of EPSC amplitude by 15-40% was seen as frequency nias incr eased from 1 to 5 Hz. The minimal latency for onset of inhibition was similar to 2 s. Stimulation at 20 Hz did not produce inhibition. 5. Th e results indicate that presynaptic muscarinic receptors are selective ly expressed by a functional subclass of preganglionic sympathetic ner ve terminals. Physiological activation of the receptors occurs during repetitive activity The extent of autoreceptor-mediated inhibition var ies as a biphasic function of stimulus frequency.