The time course of transmitter release in mouse motor nerve terminals is differentially affected by activation of muscarinic M1 or M2 receptors.

At endplates of mouse diaphragms the effects of activation of presynaptic muscarinic M1 and M2 autoreceptors on the time courses of monoquantal releases have been investigated at 20 degrees C. Quantal excitatory postsynaptic currents (qEPSCs) were elicited and recorded with a perfused macropatch electrode, through which control- and drug-containing solutions were applied to 10 microm phi regions of a neuromuscular junction. M2 receptors were activated with muscarine, while the M1 receptors were blocked by pirenzepine. M2 activation presented a slight, but highly significant augmentation of early releases. Analogously, M1 receptors were activated with muscarine, while M2 receptors were blocked by methoctramine. M1 activation elicited a highly significant small shift of the time course of release towards longer delays. In controls, the number of late releases decayed with a time constant of 0.3 ms. This time constant did not change appreciably when methoctramine or methoctramine + muscarine were applied. However, methoctramine + muscarine reduced the amplitude of qEPSCs and shortened their decay by a partial block of postsynaptic channels. Double blocks with pirenzepine + methoctramine allowed no presynaptic effect of muscarine, showing that the blocker concentrations were sufficient. Neither the addition of methoctramine to pirenzepine, nor the further addition of muscarine changed the time constant of decay of the number of late releases. The results are very similar to that of autoreceptor activations in the glutamatergic crayfish synapse: activation of inhibitory receptors augmented early releases, and that of facilitatory receptors depressed early releases [J. Dudel (2006a) Eur. J. Neurosci., 23, 2695-2700], which may suggest a general presynaptic mechanism.