Investigation of the modulation of glutamate release by sodium channels using neurotoxins
The modulation of neurotransmitter release by calcium channels is well established, yet, sodium channels were regarded mainly as charge carriers. Many lines of evidence suggest a more fine-tuning role played by sodium channels. Using rat cerebrocortical isolated nerve endings (synaptosomes) and two...
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Published in | Neuroscience Vol. 113; no. 1; pp. 115 - 123 |
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Main Authors | , , , , |
Format | Journal Article |
Language | English |
Published |
Oxford
Elsevier Ltd
01.01.2002
Elsevier |
Subjects | |
Online Access | Get full text |
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Summary: | The modulation of neurotransmitter release by calcium channels is well established, yet, sodium channels were regarded mainly as charge carriers. Many lines of evidence suggest a more fine-tuning role played by sodium channels. Using rat cerebrocortical isolated nerve endings (synaptosomes) and two toxins that have separate sites of action on sodium channels and provoke distinct changes in channel kinetics, we were able to show that depending on the rate of increase in channel conductance, the outcome in terms of neurotransmitter release and calcium channel types coupled to that event are different. Mainly, our study focused on veratridine, an alkaloid from lilaceous plants that binds to sodium channel toxin site 2, and tityustoxin, a toxin purified from the venom of the Brazilian yellow scorpion
Tityus serrulatus that binds to site 3. Veratridine induces a slower increase in intrasynaptosomal sodium and calcium concentrations, slower depolarization, delayed exocytosis and a slower and predominantly calcium-independent glutamate release, when compared to tityustoxin.
Thus, we have used these two toxins to investigate the events that start with sodium entry and culminate with the release of glutamate in isolated nerve endings (synaptosomes) from rat cerebral cortex. With that in mind we measured intrasynaptosomal free sodium concentration [Na
+]
i, intrasynaptosomal free calcium concentration [Ca
2+]
i, membrane potential, exocytosis and glutamate release using fluorescent probes. |
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Bibliography: | ObjectType-Article-2 SourceType-Scholarly Journals-1 ObjectType-Feature-1 content type line 23 |
ISSN: | 0306-4522 1873-7544 |
DOI: | 10.1016/S0306-4522(02)00139-2 |