EFFECTS OF MUSCARINIC RECEPTOR STIMULATION OF SYMPATHETIC PREGANGLIONIC NEURONS OF NEONATAL RAT SPINAL-CORD IN-VITRO

Whole cell current-clamp recordings were made from 85 sympathetic preg anglionic neurones (SPN) of the neonatal spinal cord in vitro. Superfu sion of up to 500 mu M acetylcholine (2-30 sec) gave weak responses. C arbachol (CChol; 5-50 mu M) superfused for 1-20 sec, hyperpolarized SP N. This response was associated with a mean reduction in input resista nce of 22%. Ion substitution studies suggested that potassium is the l ikely carrier of at least part of the current underlying the CChol-ind uced hyperpolarization. Some SPN display spontaneous rhythmic oscillat ions in their membrane potentials which may be due to action potential discharge in electrically-coupled neurones. CChol also acts to inhibi t these oscillations concomitant with the hyperpolarization. Responses to CChol were unaffected by addition of 500 nM TTX to the bathing med ium suggesting that CChol acts directly upon SPN. Carbachol-induced hy perpolarizing responses were totally abolished by the non-specific mus carinic receptor antagonist atropine (20-50 mu M). Pirenzepine, at con centrations over 5 mu M reversibly reduced the responses to CChol. Gal lamine, an M2 receptor antagonist applied at 25 mu M also reversibly a bolished the CChol responses. These results suggest that CChol-mediate d hyperpolarizations may be due to M2 receptor activation.