Abstract
Glutamate concentration increases significantly in the extracellular compartment during brain ischaemia and anoxia. This increase has an important Ca(2+)-independent component, which is due in part to the reversal of glutamate transporters of the plasma membrane of neurons and glia. The toxin phoneutriatoxin 3-4 (Tx3-4) from the spider Phoneutria nigriventer has been reported to decrease the evoked glutamate release from synaptosomes by inhibiting Ca(2+) entry via voltage-dependent Ca(2+) channels. However, we report here that Tx3-4 is also able to inhibit the uptake of glutamate by synaptosomes in a time-dependent manner and that this inhibition in turn leads to a decrease in the Ca(2+)-independent release of glutamate. No other polypeptide toxin so far described has this effect. Our results suggest that Tx3-4 can be a valuable tool in the investigation of function and dysfunction of glutamatergic neurotransmission in diseases such as ischaemia.
Publication types
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Research Support, Non-U.S. Gov't
MeSH terms
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ATP-Binding Cassette Transporters / antagonists & inhibitors
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ATP-Binding Cassette Transporters / metabolism
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Amino Acid Transport System X-AG
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Animals
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Binding, Competitive
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Biological Transport / drug effects
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Calcium / pharmacology
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Calcium Channel Blockers / pharmacology
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Dose-Response Relationship, Drug
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Egtazic Acid / pharmacology
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Glutamic Acid / metabolism*
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Glutamic Acid / pharmacology
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Hippocampus / cytology
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Neuropeptides / pharmacology*
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Neurotoxins / pharmacology*
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Peptides / pharmacology*
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Potassium Chloride / antagonists & inhibitors
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Potassium Chloride / pharmacology
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Rats
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Rats, Wistar
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Spiders*
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Synaptosomes / drug effects*
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Synaptosomes / metabolism
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Veratridine / antagonists & inhibitors
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Veratridine / pharmacology
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omega-Conotoxins*
Substances
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ATP-Binding Cassette Transporters
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Amino Acid Transport System X-AG
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Calcium Channel Blockers
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Neuropeptides
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Neurotoxins
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Peptides
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Tx3 neurotoxin
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omega-Conotoxins
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omega-conotoxin-MVIIC
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Glutamic Acid
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Egtazic Acid
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Potassium Chloride
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Veratridine
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Calcium