Antillatoxin is a marine cyanobacterial toxin that potently activates voltage-gated sodium channels
| Autor: | William H. Gerwick, Thomas F. Murray, Fumiaki Yokokawa, Tatsufumi Okino, Frederick W. Berman, T. Shioiri, W. I. Li |
|---|---|
| Rok vydání: | 2001 |
| Předmět: |
Cell Survival
Lipoproteins Tetrodotoxin Biology Cyanobacteria Binding Competitive Peptides Cyclic Sodium Channels Rats Sprague-Dawley Lipopeptides Brevetoxin chemistry.chemical_compound Cerebellum Nitriles Pyrethrins Animals Neurotoxin Batrachotoxins Cells Cultured Neurons Multidisciplinary Sodium channel Biological Sciences Antillatoxin Rats Kinetics Sea Anemones chemistry Biochemistry Biophysics NMDA receptor Calcium Marine Toxins Batrachotoxin Marine toxin |
| Zdroj: | Proceedings of the National Academy of Sciences. 98:7599-7604 |
| ISSN: | 1091-6490 0027-8424 |
| DOI: | 10.1073/pnas.121085898 |
| Popis: | Antillatoxin (ATX) is a lipopeptide derived from the pantropical marine cyanobacterium Lyngbya majuscula . ATX is neurotoxic in primary cultures of rat cerebellar granule cells, and this neuronal death is prevented by either N- methyl- d -aspartate (NMDA) receptor antagonists or tetrodotoxin. To further explore the potential interaction of ATX with voltage-gated sodium channels, we assessed the influence of tetrodotoxin on ATX-induced Ca 2+ influx in cerebellar granule cells. The rapid increase in intracellular Ca 2+ produced by ATX (100 nM) was antagonized in a concentration-dependent manner by tetrodotoxin. Additional, more direct, evidence for an interaction with voltage-gated sodium channels was derived from the ATX-induced allosteric enhancement of [ 3 H]batrachotoxin binding to neurotoxin site 2 of the α subunit of the sodium channel. ATX, moreover, produced a strong synergistic stimulation of [ 3 H]batrachotoxin binding in combination with brevetoxin, which is a ligand for neurotoxin site 5 on the voltage-gated sodium channel. Positive allosteric interactions were not observed between ATX and either α-scorpion toxin or the pyrethroid deltamethrin. That ATX interaction with voltage-gated sodium channels produces a gain of function was demonstrated by the concentration-dependent and tetrodotoxin-sensitive stimulation of 22 Na + influx in cerebellar granule cells exposed to ATX. Together these results demonstrate that the lipopeptide ATX is an activator of voltage-gated sodium channels. The neurotoxic actions of ATX therefore resemble those of brevetoxins that produce neural insult through depolarization-evoked Na + load, glutamate release, relief of Mg 2+ block of NMDA receptors, and Ca 2 + influx. |
| Databáze: | OpenAIRE |
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