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Voltage-gated sodium channels (VGSCs) are important for action potentials. There are seven major isoforms of the pore-forming and gate-bearing α-subunit (NaV 1) of VGSCs in mammalian neurons, and a given neuron can express more than one isoform. Five of the neuronal isoforms, NaV 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 NaV 1.1 through 1.8 expressed inXenopus oocytes. Although none blocked NaV 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 NaV 1.6 and 1.7, respectively. Ruled out as major players in both fiber types were NaV 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 NaV 1 isoforms responsible for propagating action potentials in peripheral nerve. The panel of μ-conopeptides should be useful in identifying the functional contributions of NaV 1 isoforms in other preparations.

proceedings of the national academy of sciences of the united states of america

μ-Conotoxins that differentially block sodium channels Na <sub>V</sub> 1.1 through 1.8 identify those responsible for action potentials in sciatic nerve

μ-Conotoxins that differentially block sodium channels Na V 1.1 through 1.8 identify those responsible for action potentials in sciatic nerve

μ-Conotoxins that differentially block sodium channels Na _V 1.1 through 1.8 identify those responsible for action potentials in sciatic nerve