• 1
    Presynaptic effects of muscarine on neurotransmitter release were studied at the frog neuromuscular junction, using focal depolarization of the presynaptic terminal to different levels.
  • 2
    Muscarine (10 μM) had a dual effect on ACh release: concomitant inhibition and enhancement of release at the same patch of presynaptic membrane.
  • 3
    These two effects were maximal at low depolarizing pulses and diminished as depolarization increased.
  • 4
    At low depolarizing pulses, atropine (1 μM) enhanced release, suggesting that ACh in the synaptic cleft causes a net tonic inhibition of ACh release.
  • 5
    In the presence of the M2 antagonist methoctramine (1 μM), muscarine (10 μM) enhanced ACh release.
  • 6
    In the presence of the M1 antagonist pirenzepine (10 μM), muscarine (10 μM) produced stronger inhibition.
  • 7
    These results show that the M2 receptor is responsible for inhibition of ACh release, while the M1 receptor is responsible for its enhancement.
  • 8
    The inhibitory effect of muscarine did not depend on extracellular [Ca2+]. Enhancement of release was abolished at low extracellular [Ca2+].
  • 9
    The muscarine inhibitory effect was not associated with a reduction of Ca2+ current, while release enhancement was associated with an increase of Ca2+ current.