Effect of veratridine on miniature endplate current amplitudes at the rat neuromuscular junction and acetylcholine uptake by Torpedo synaptic vesicles.
Veratridine produces a marked elevation in spontaneous quantal release from nerve endings through its ability to enhance sodium-channel activity, leading to sustained membrane depolarization. In the course of an electrophysiological investigation into the effects of vesamicol, an inhibitor of the synaptic vesicle acetylcholine transporter, on veratridine-induced acetylcholine release from rat motor nerve terminals we observed that veratridine itself has an effect on miniature endplate current amplitude distributions suggestive of an effect of the compound on the filling of cholinergic synaptic vesicles with acetylcholine. This effect of veratridine is release-dependent, being inhibited by either removal of extracellular calcium ions or by the addition of the sodium channel blocking toxin, tetrodotoxin. Biochemical studies using synaptic vesicles isolated from Torpedo electroplaque confirmed the ability of veratridine to directly inhibit the vesicular transport of acetylcholine. This appears to be a consequence of its ability to dissipate the trans-vesicular membrane proton gradient, which normally drives the active transport of acetylcholine into synaptic vesicles. We discuss how such an action of veratridine could lead to the observed release-dependent effects of the compound on electrophysiologically monitored spontaneous quantal acetylcholine release. The action of veratridine on cholinergic synaptic vesicles could be of considerable import when using this agent to elicit neurotransmitter release from either peripheral or central nerve endings.
Pemberton
K E
KE
Department of Physiology and Pharmacology, University of Strathclyde, Glasgow, Scotland, UK.
Nguyen
M L
ML
Prior
C
C
Parsons
S M
SM
Marshall
I G
IG
D000109:Acetylcholine / Q000378:metabolism*; D000818:Animals; D004557:Electric Organ / Q000187:drug effects / Q000294:innervation / Q000378:metabolism; D004594:Electrophysiology; D006863:Hydrogen-Ion Concentration; D066298:In Vitro Techniques; D008297:Male; D008564:Membrane Potentials / Q000187:drug effects; D009045:Motor Endplate / Q000187:drug effects*; D018485:Muscle Fibers, Skeletal / Q000187:drug effects; D009467:Neuromuscular Depolarizing Agents / Q000494:pharmacology; D009469:Neuromuscular Junction / Q000187:drug effects*; D010880:Piperidines / Q000494:pharmacology; D051381:Rats; D017207:Rats, Sprague-Dawley; D013572:Synaptic Vesicles / Q000187:drug effects / Q000378:metabolism*; D013779:Tetrodotoxin / Q000494:pharmacology; D014101:Torpedo / Q000378:metabolism*; D014701:Veratridine / Q000494:pharmacology*
D009467:Neuromuscular Depolarizing Agents; D010880:Piperidines; C006189:vesamicol; D013779:Tetrodotoxin; D014701:Veratridine; D000109:Acetylcholine