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Potentiation by 4‐aminopyridine of quantal acetylcholine release at the Torpedo nerve‐electroplaque junction.
Author(s) -
Muller D
Publication year - 1986
Publication title -
the journal of physiology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.802
H-Index - 240
eISSN - 1469-7793
pISSN - 0022-3751
DOI - 10.1113/jphysiol.1986.sp016265
Subject(s) - 4 aminopyridine , tetrodotoxin , tetraethylammonium , acetylcholine , chemistry , electrophysiology , long term potentiation , depolarization , biophysics , neuromuscular junction , neurotransmission , neuroscience , potassium channel , endocrinology , medicine , biology , potassium , receptor , biochemistry , organic chemistry
The effects of 4‐aminopyridine (4‐AP) on electrophysiological post‐synaptic responses evoked by field stimulation or evoked focally using a loose patch‐clamp technique, and on radiolabelled transmitter release were studied in the Torpedo electric organ. In this preparation, 4‐AP had three major effects: it greatly potentiated the amount of acetylcholine (ACh) released by a nerve impulse, it prolonged the duration of the post‐synaptic electroplaque current (e.c.) by several hundreds of milliseconds, and it increased the delay of responses triggered by a presynaptic action potential. Noise analysis performed at different times during the focally recorded giant response showed that it was made of a sustained release of ACh quanta. The maximum synchronous release of transmitter, expressed as the maximum number of quanta simultaneously delivered/micron2 of presynaptic membrane, was apparently not modified by 4‐AP. A slightly different dose dependence was found for the effects of 4‐AP on the potentiation of transmitter release and on the prolongation of the synaptic delay. The effects of tetraethylammonium (TEA) and other K+ channel blockers on these parameters were similar to those of 4‐AP. Strong depolarizing pulses applied focally to a nerve ending were able to evoke a giant response even in the presence of 1 microM‐tetrodotoxin (TTX). The prolongation of the discharge by 4‐AP was therefore not caused by repetitive re‐excitation of the nerve branches. Both the amplitude and the time course of the giant response were Ca2+ dependent. At a low Mg2+ concentration, the Ca2+ dependence of transmitter release was identical in the presence or absence of 4‐AP. Paradoxically, in the presence of 4‐AP, addition of 4 mM‐Mg2+ considerably increased the Ca2+ dependence of release, whereas in the absence of 4‐AP, Mg2+ blocked transmitter release by decreasing its sensitivity to Ca2+. This potentiating interaction between Mg2+ and 4‐AP was not seen with TEA or guanidine. In conclusion, 4‐AP potentiates ACh release in two different ways in the Torpedo electric organ: it promotes a sustained quantal release of transmitter during several hundreds of milliseconds without any significant change in the maximal synchronous release, it interacts with Mg2+ in such a manner that the sensitivity to Ca2+ of the nerve terminals is increased.