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• W2118129389 abstract "Voltage-gated sodium channels (VGSCs) are important for action potentials. There are seven major isoforms of the pore-forming and gate-bearing α-subunit (Na V 1) of VGSCs in mammalian neurons, and a given neuron can express more than one isoform. Five of the neuronal isoforms, Na V 1.1, 1.2, 1.3, 1.6, and 1.7, are exquisitely sensitive to tetrodotoxin (TTX), and a functional differentiation of these presents a serious challenge. Here, we examined a panel of 11 μ-conopeptides for their ability to block rodent Na V 1.1 through 1.8 expressed in Xenopus oocytes. Although none blocked Na V 1.8, a TTX-resistant isoform, the resulting “activity matrix” revealed that the panel could readily discriminate between the members of all pair-wise combinations of the tested isoforms. To examine the identities of endogenous VGSCs, a subset of the panel was tested on A- and C-compound action potentials recorded from isolated preparations of rat sciatic nerve. The results show that the major subtypes in the corresponding A- and C-fibers were Na V 1.6 and 1.7, respectively. Ruled out as major players in both fiber types were Na V 1.1, 1.2, and 1.3. These results are consistent with immunohistochemical findings of others. To our awareness this is the first report describing a qualitative pharmacological survey of TTX-sensitive Na V 1 isoforms responsible for propagating action potentials in peripheral nerve. The panel of μ-conopeptides should be useful in identifying the functional contributions of Na V 1 isoforms in other preparations." @default.
• W2118129389 created "2016-06-24" @default.
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• W2118129389 date "2011-06-07" @default.
• W2118129389 modified "2023-10-08" @default.
• W2118129389 title "μ-Conotoxins that differentially block sodium channels Na _V 1.1 through 1.8 identify those responsible for action potentials in sciatic nerve" @default.
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• W2118129389 doi "https://doi.org/10.1073/pnas.1107027108" @default.
• W2118129389 hasPubMedCentralId "https://www.ncbi.nlm.nih.gov/pmc/articles/3121861" @default.
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• W2118129389 hasPublicationYear "2011" @default.
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