Ca2+-Independent Feedback Inhibition of Acetylcholine Release in Frog Neuromuscular Junction

Inna Slutsky, Grigory Rashkovan, Hanna Parnas, Itzchak Parnas*

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

27 Scopus citations

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 (Ki) of the presynaptic M2 muscarinic receptor. The Ki for muscarine shifts from ∼0.23 μM (at resting potential) to ∼8 μM (at a high depolarization). Measurements of Ca2+ currents in axon terminals showed that the depolarization-mediated shift in Ki does not stem from depolarization-dependent changes in Ca2+ influx. Pretreatments with pertussis toxin (PTX) abolished the depolarization-dependent shift in Ki; at all depolarizations Ki was the same and higher (∼32 μM) 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.

Original languageEnglish
Pages (from-to)3426-3433
Number of pages8
JournalJournal of Neuroscience
Volume22
Issue number9
DOIs
StatePublished - 1 May 2002

Keywords

  • Ca currents
  • Ca-independent inhibition
  • Fast and slow inhibition
  • Feedback inhibition
  • Frog neuromuscular junction
  • M muscarinic presynaptic receptor

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