title: Ca2+-independent feedback inhibition of acetylcholine release in frog neuromuscular junction.
abstract: The effect of membrane potential on feedback inhibition of acetylcholine (ACh) release was studied using the frog neuromuscular junction. It was found that membrane potential affects the functional affinity (K(i)) of the presynaptic M2 muscarinic receptor. The K(i) for muscarine shifts from approximately 0.23 microm (at resting potential) to approximately 8 microm (at a high depolarization). Measurements of Ca2+ currents in axon terminals showed that the depolarization-mediated shift in K(i) does not stem from depolarization-dependent changes in Ca2+ influx. Pretreatments with pertussis toxin (PTX) abolished the depolarization-dependent shift in K(i); at all depolarizations K(i) was the same and higher (approximately 32 microm) than before PTX treatment. The inhibitory effect of muscarine on ACh release is produced by two independent mechanisms: a slow, PTX-sensitive process, which prevails at low to medium depolarizations and operates already at low muscarine concentrations, and a fast, PTX-insensitive and voltage-independent process, which requires higher muscarine concentrations. Neither of the two processes involves a reduction in Ca2+ influx.
authors.affiliation: The Otto Loewi Minerva Center for Cellular and Molecular Neurobiology, Department of Neurobiology, The Hebrew University, Jerusalem 91904, Israel.
authors.forename: Inna
authors.initials: I
authors.lastname: Slutsky
authors.forename: Grigory
authors.initials: G
authors.lastname: Rashkovan
authors.forename: Hanna
authors.initials: H
authors.lastname: Parnas
authors.forename: Itzchak
authors.initials: I
authors.lastname: Parnas
mesh_terms: D000109:Acetylcholine / Q000378:metabolism*; D000200:Action Potentials / Q000502:physiology; D000818:Animals; D002118:Calcium / Q000378:metabolism*; D004305:Dose-Response Relationship, Drug; D004558:Electric Stimulation; D019706:Excitatory Postsynaptic Potentials / Q000187:drug effects / Q000502:physiology; D025461:Feedback, Physiological / Q000187:drug effects / Q000502:physiology*; D019204:GTP-Binding Proteins / Q000187:drug effects / Q000378:metabolism; D066298:In Vitro Techniques; D008564:Membrane Potentials / Q000187:drug effects / Q000502:physiology; D009116:Muscarine / Q000494:pharmacology; D018721:Muscarinic Agonists / Q000494:pharmacology; D009433:Neural Inhibition / Q000187:drug effects / Q000502:physiology; D009469:Neuromuscular Junction / Q000187:drug effects / Q000378:metabolism*; D018408:Patch-Clamp Techniques; D037342:Pertussis Toxin; D011188:Potassium / Q000378:metabolism; D017729:Presynaptic Terminals / Q000187:drug effects / Q000378:metabolism; D011895:Rana ridibunda; D043585:Receptor, Muscarinic M2; D011976:Receptors, Muscarinic / Q000378:metabolism; D013779:Tetrodotoxin / Q000494:pharmacology; D010566:Virulence Factors, Bordetella / Q000494:pharmacology
chemical_list: D018721:Muscarinic Agonists; D043585:Receptor, Muscarinic M2; D011976:Receptors, Muscarinic; D010566:Virulence Factors, Bordetella; D013779:Tetrodotoxin; D009116:Muscarine; D037342:Pertussis Toxin; D019204:GTP-Binding Proteins; D000109:Acetylcholine; D011188:Potassium; D002118:Calcium