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 Ca2+ influx in cerebellar granule cells. The rapid increase in intracellular Ca2+ 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 [3H]batrachotoxin binding to neurotoxin site 2 of the alpha subunit of the sodium channel. ATX, moreover, produced a strong synergistic stimulation of [3H]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 alpha-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 22Na+ 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 Mg2+ block of NMDA receptors, and Ca2+ influx.
Pharmacology, Toxicology and Pharmaceutical Science
9
12%
Biochemistry, Genetics and Molecular Biology
9
12%
Social Sciences
3
4%
Other
10
13%
Unknown
15
20%
Attention Score in Context
Attention Score in Context
This research output has an Altmetric Attention Score of 6. This is our high-level measure of the quality and quantity of online attention that it has received. This Attention Score, as well as the ranking and number of research outputs shown below, was calculated when the research output was last mentioned on 12 October 2015.
All research outputs
#7,701,553
of 34,826,706 outputs
Outputs from Proceedings of the National Academy of Sciences of the United States of America
#64,080
of 119,817 outputs
Outputs of similar age
#14,521
of 60,908 outputs
Outputs of similar age from Proceedings of the National Academy of Sciences of the United States of America
#228
of 516 outputs
Altmetric has tracked 34,826,706 research outputs across all sources so far. This one has received more attention than most of these and is in the 73rd percentile.
So far Altmetric has tracked 119,817 research outputs from this source. They typically receive a lot more attention than average, with a mean Attention Score of 40.2. This one is in the 37th percentile – i.e., 37% of its peers scored the same or lower than it.
Older research outputs will score higher simply because they've had more time to accumulate mentions. To account for age we can compare this Altmetric Attention Score to the 60,908 tracked outputs that were published within six weeks on either side of this one in any source. This one has gotten more attention than average, scoring higher than 60% of its contemporaries.
We're also able to compare this research output to 516 others from the same source and published within six weeks on either side of this one. This one is in the 37th percentile – i.e., 37% of its contemporaries scored the same or lower than it.
