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

Inna Slutsky, Grigory Rashkovan, Hanna Parnas, Itzchak Parnas
2002 Journal of Neuroscience  
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 M 2 muscarinic receptor. The K i for muscarine shifts from ϳ0.23 M (at resting potential) to ϳ8 M (at a high depolarization). Measurements of Ca 2ϩ currents in axon terminals showed that the depolarizationmediated shift in K i does not stem from
more » ... ent changes in Ca 2ϩ influx. Pretreatments with pertussis toxin (PTX) abolished the depolarization-dependent shift in K i ; at all depolarizations K i was the same and higher (ϳ32 M) 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 Ca 2ϩ influx.
doi:10.1523/jneurosci.22-09-03426.2002 pmid:11978819 fatcat:5drbrwxb55evzli6rovvv42nbi