μ-Conotoxins that differentially block sodium channels Na V 1.1 through 1.8 identify those responsible for action potentials in sciatic nerve
| Autor: | Min Min Zhang, Layla Azam, Baldomero M. Olivera, Michael J. Wilson, Joanna Gajewiak, Doju Yoshikami, Grzegorz Bulaj |
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| Rok vydání: | 2011 |
| Předmět: |
Gene isoform
Patch-Clamp Techniques Neurotoxins Xenopus Action Potentials Biology Sodium Channels Xenopus laevis chemistry.chemical_compound medicine Animals Protein Isoforms Patch clamp Conotoxin Multidisciplinary Sodium channel Anatomy Biological Sciences biology.organism_classification Sciatic Nerve Rats Cell biology medicine.anatomical_structure chemistry Oocytes Tetrodotoxin Sciatic nerve Neuron Conotoxins Sodium Channel Blockers |
| Zdroj: | Proceedings of the National Academy of Sciences. 108:10302-10307 |
| ISSN: | 1091-6490 0027-8424 |
| DOI: | 10.1073/pnas.1107027108 |
| Popis: | 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. |
| Databáze: | OpenAIRE |
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