This review highlights a newly discovered structural site in the P-region of domain IV that imparts tetrodotoxin resistance in voltage-gated sodium channels.
Tetrodotoxin (TTX) is a highly specific blocker of voltage-gated sodium channels. The dissociation constant of block varies with different channel isoforms. Until recently, channel resistance was thought to be primarily imparted by amino acid substitutions at a single position in domain I. Recent work reveals a novel site for tetrodotoxin resistance in the P-region of domain IV.
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Geffeney et al. (2006) studied this question.
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