2020
DOI: 10.1016/j.neulet.2020.134853
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The voltage-gated sodium channel inhibitor, 4,9-anhydrotetrodotoxin, blocks human Nav1.1 in addition to Nav1.6

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Cited by 21 publications
(18 citation statements)
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“…47 Although there was a small proportion of small-sized to medium-sized neurons that were blocked by 4,9 AH TTX, we could not determine whether they were nociceptors because of methodological limitations, specifically our indiscriminate mechanical receptive field search criteria and the small numbers of cold neurons that could be recruited electrically. A potential caveat of this finding is that the concentration of 4,9 AH TTX required for efficacy in our nerve prep (3 µM) is not selective for the Na v 1.1 and Na v 1.6 channels in vitro , 8,35 and thus, we cannot rule out the effects of block of other Na v s at this concentration. However , it seems likely that higher concentrations of blockers, which may be more than their IC50s for channels in vitro, are required in vivo because of diffusion barriers.…”
Section: Discussionmentioning
confidence: 87%
“…47 Although there was a small proportion of small-sized to medium-sized neurons that were blocked by 4,9 AH TTX, we could not determine whether they were nociceptors because of methodological limitations, specifically our indiscriminate mechanical receptive field search criteria and the small numbers of cold neurons that could be recruited electrically. A potential caveat of this finding is that the concentration of 4,9 AH TTX required for efficacy in our nerve prep (3 µM) is not selective for the Na v 1.1 and Na v 1.6 channels in vitro , 8,35 and thus, we cannot rule out the effects of block of other Na v s at this concentration. However , it seems likely that higher concentrations of blockers, which may be more than their IC50s for channels in vitro, are required in vivo because of diffusion barriers.…”
Section: Discussionmentioning
confidence: 87%
“…This toxin can cause fatal food poisoning in humans. TTX is an important pharmacological tool that blocks voltage-gated sodium channels (Na v ) with high specificity and is a widely used as an antipredator defense in metazoans . TTX possesses a complex and rare structure consisting of a 2,4-dioxaadamantane skeleton and a cyclic guanidine.…”
mentioning
confidence: 53%
“…The reason for the discrepancy in the proportion of nociceptors blocked by PF007 between electrophysiological and calcium imaging experiments was not clear and therefore we decided to use a different class of sodium channel blocker to further investigate this. Due to the limited availability of Nav1.7 selective inhibitors in the mouse, we used 4,9 AH TTX, a selective blocker of Nav1.1 and Nav1.6 [10; 39], and then blocked Nav1.7 in addition to these channels with TTX. The population dependent on Nav1.7 for propagation can be estimated by subtracting the number of neurons blocked after 4,9 AH TTX from the total blocked after subsequent TTX application.…”
Section: Resultsmentioning
confidence: 99%