MUSCARINIC MODULATION OF NEUROTRANSMISSION - THE EFFECTS OF SOME AGONISTS AND ANTAGONISTS

1. Functional studies were performed to evaluate the effects of some m uscarinic agents at the neuromuscular junction of the mouse. 2. The pr esynaptic control of acetylcholine release and the postsynaptic activa tion of the nicotinic receptor have been analyzed by means of extracel lular recording. The amplitude of spontaneous and of evoked acetylchol ine release, the frequency of spontaneous acetylcholine release and th e time course of the quantal release have been measured by means of an EPC7 patch clamp amplifier. 3. This electrophysiological method revea led multiple dose-related effects of some agonists and antagonists on the above parameters. Concentration-response curves related to the par ameters underlying the function of this cholinergic synapse were obtai ned and the apparent EC50 values calculated. 4. Many of the interactio ns of the agonists and antagonists could inhibit neuromuscular transmi ssion. The rank order potencies related to the inhibition of the evoke d signals were carbachol > oxotremorine > d,l-muscarine for the agonis ts and methoctramine > 4-DAMP > l-hyoscyamine > AFDX-116 > ipratropium > pirenzepine for the antagonists. 5. These findings suggest a more c omplicated pattern related to the muscarinic action at the mouse neuro muscular junction with the involvement of some post-synaptic located s ites.