{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,29]],"date-time":"2026-09-29T20:22:00Z","timestamp":1790713320359,"version":"4.1.0"},"reference-count":32,"publisher":"National Academy of Sciences","issue":"13","content-domain":{"domain":["www.pnas.org"],"crossmark-restriction":true},"short-container-title":["Proc. Natl. Acad. Sci. U.S.A."],"published-print":{"date-parts":[[2001,6,19]]},"abstract":"<jats:p>\n                    Antillatoxin (ATX) is a lipopeptide derived from the pantropical marine cyanobacterium\n                    <jats:italic>Lyngbya majuscula<\/jats:italic>\n                    . ATX is neurotoxic in primary cultures of rat cerebellar granule cells, and this neuronal death is prevented by either\n                    <jats:italic>N-<\/jats:italic>\n                    methyl-\n                    <jats:sc>d<\/jats:sc>\n                    -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\n                    <jats:sup>2+<\/jats:sup>\n                    influx in cerebellar granule cells. The rapid increase in intracellular Ca\n                    <jats:sup>2+<\/jats:sup>\n                    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 [\n                    <jats:sup>3<\/jats:sup>\n                    H]batrachotoxin binding to neurotoxin site 2 of the \u03b1 subunit of the sodium channel. ATX, moreover, produced a strong synergistic stimulation of [\n                    <jats:sup>3<\/jats:sup>\n                    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 \u03b1-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\n                    <jats:sup>22<\/jats:sup>\n                    Na\n                    <jats:sup>+<\/jats:sup>\n                    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\n                    <jats:sup>+<\/jats:sup>\n                    load, glutamate release, relief of Mg\n                    <jats:sup>2+<\/jats:sup>\n                    block of NMDA receptors, and Ca\n                    <jats:sup>2 +<\/jats:sup>\n                    influx.\n                  <\/jats:p>","DOI":"10.1073\/pnas.121085898","type":"journal-article","created":{"date-parts":[[2002,7,26]],"date-time":"2002-07-26T10:45:09Z","timestamp":1027680309000},"page":"7599-7604","update-policy":"https:\/\/doi.org\/10.1073\/pnas.cm10313","source":"Crossref","is-referenced-by-count":99,"title":["Antillatoxin is a marine cyanobacterial toxin that potently activates voltage-gated sodium channels"],"prefix":"10.1073","volume":"98","author":[{"given":"W. I.","family":"Li","sequence":"first","affiliation":[{"name":"Department of Physiology and Pharmacology, College of Veterinary Medicine, University of Georgia, Athens, GA 30602-7389; College of Pharmacy, Oregon State University, Corvallis, OR 97331; and Faculty of Pharmaceutical Sciences, Nagoya City University, Tanabe-dori, Mizuho-ku, Nagoya 467-8603, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"F. 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