Factors governing the appearance of small-mode miniature endplate currents at the snake neuromuscular junction.
At the snake neuromuscular junction, following a short period of high frequency motor nerve stimulation, a population of 'small-mode' miniature endplate currents (MEPCs) is seen. These small-mode MEPCs are believed to be due to the release of acetylcholine from incompletely refilled recycling synaptic vesicles [Searl et al., Neuroscience, 35 (1991) 145-156]. This study determines the role of the trans-vesicular membrane proton gradient in the generation of small-mode MEPCs. Preserving the trans-vesicular membrane proton gradient during synaptic vesicle exocytosis by exposure of snake nerve/muscle preparations to an extracellular pH approximately equal to the intravesicular pH, leads to an augmentation of the amplitude of the stimulation-induced small-mode MEPCs. Conversely, pretreatment of snake neuromuscular preparations with 10 mM ammonium ions, to buffer intravesicular protons and hence dissipate the trans-vesicular membrane proton gradient, leads to an inhibition of the stimulation-induced appearance of small-mode MEPCs. The data are consistent with the theory that the reduced acetylcholine content of recycled synaptic vesicles in the snake is a consequence of an incomplete restoration of the trans-vesicular membrane proton gradient following synaptic vesicle exocytosis. Thus, in recycling synaptic vesicles the limiting step in the refilling process appears to be generation of the trans-membrane proton gradient and not the transport of acetylcholine into the vesicle.
Prior
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Department of Physiology and Pharmacology, University of Strathclyde, Glasgow, Scotland, UK.
D000643:Ammonium Chloride / Q000494:pharmacology; D000818:Animals; D017812:Colubridae / Q000502:physiology*; D004558:Electric Stimulation; D006863:Hydrogen-Ion Concentration; D008564:Membrane Potentials / Q000187:drug effects / Q000502:physiology; D009045:Motor Endplate / Q000187:drug effects / Q000502:physiology*; D009046:Motor Neurons / Q000187:drug effects / Q000502:physiology*; D016011:Normal Distribution; D011522:Protons; D013572:Synaptic Vesicles / Q000187:drug effects / Q000502:physiology*
D011522:Protons; D000643:Ammonium Chloride