Glycerotoxin stimulates neurotransmitter release from N-type Ca2+ channel expressing neurons

Schenning, Mitja, Proctor, Dustin T., Ragnarsson, Lotten, Barbier, Julien, Lavidis, Nickolas A., Molgo, Jordi J., Zamponi, Gerald W., Schiavo, Giampietro and Meunier, Frederic A. (2006) Glycerotoxin stimulates neurotransmitter release from N-type Ca2+ channel expressing neurons. Journal of Neurochemistry, 98 3: 894-904. doi:10.1111/j.1471-4159.2006.03938.x


Author Schenning, Mitja
Proctor, Dustin T.
Ragnarsson, Lotten
Barbier, Julien
Lavidis, Nickolas A.
Molgo, Jordi J.
Zamponi, Gerald W.
Schiavo, Giampietro
Meunier, Frederic A.
Title Glycerotoxin stimulates neurotransmitter release from N-type Ca2+ channel expressing neurons
Formatted title
Glycerotoxin stimulates neurotransmitter release from N-type Ca2+ channel expressing neurons
Journal name Journal of Neurochemistry   Check publisher's open access policy
ISSN 0022-3042
Publication date 2006-08
Sub-type Article (original research)
DOI 10.1111/j.1471-4159.2006.03938.x
Volume 98
Issue 3
Start page 894
End page 904
Total pages 11
Editor Anthony J. Turner
Brian Collier
Place of publication United Kingdom
Publisher Blackwell Publishing
Collection year 2006
Language eng
Subject 11 Medical and Health Sciences
1109 Neurosciences
C1
Formatted abstract
Glycerotoxin (GLTx) is capable of stimulating neurotransmitter release at the frog neuromuscular junction by directly interacting with N-type Ca2+ (Ca v2.2) channels. Here we have utilized GLTx as a tool to investigate the functionality of Cav2.2 channels in various mammalian neuronal preparations. We first adapted a fluorescent-based high-throughput assay to monitor glutamate release from rat cortical synaptosomes. GLTx potently stimulates glutamate secretion and Ca2+ influx in synaptosomes with an EC50 of 50 pM. Both these effects were prevented using selective Cav2.2 channel blockers suggesting the functional involvement of Cav2.2 channels in mediating glutamate release in this system. We further show that both Cav2.1 (P/Q-type) and Cav2.2 channels contribute equally to depolarization-induced glutamate release. We then investigated the functionality of Cav2.2 channels at the neonatal rat neuromuscular junction. GLTx enhances both spontaneous and evoked neurotransmitter release causing a significant increase in the frequency of postsynaptic action potentials. These effects were blocked by specific Cav2.2 channel blockers demonstrating that either GLTx or its derivatives could be used to selectively enhance the neurotransmitter release from Cav2.2-expressing mammalian neurons.
Keyword Biochemistry & Molecular Biology
Neurosciences
Conotoxin
Exocytosis
Glycerotoxin
N-type Ca2+ Channel
Neuromuscular Junction
Familial Hemiplegic Migraine
Frog Neuromuscular-junction
Episodic Ataxia Type-2
Calcium-channels
Alpha-latrotoxin
Q-Index Code C1
Q-Index Status Provisional Code
Institutional Status UQ

 
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Created: Wed, 15 Aug 2007, 07:59:27 EST