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