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Proc Natl Acad Sci U S A
2011 Jun 21;10825:10302-7. doi: 10.1073/pnas.1107027108.
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μ-Conotoxins that differentially block sodium channels NaV1.1 through 1.8 identify those responsible for action potentials in sciatic nerve.
Wilson MJ
,
Yoshikami D
,
Azam L
,
Gajewiak J
,
Olivera BM
,
Bulaj G
,
Zhang MM
.
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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 (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.
Akopian,
A tetrodotoxin-resistant voltage-gated sodium channel expressed by sensory neurons.
1996, Pubmed,
Xenbase
Akopian,
A tetrodotoxin-resistant voltage-gated sodium channel expressed by sensory neurons.
1996,
Pubmed
,
Xenbase
Billen,
Animal peptides targeting voltage-activated sodium channels.
2008,
Pubmed
Black,
Tetrodotoxin-resistant sodium channels Na(v)1.8/SNS and Na(v)1.9/NaN in afferent neurons innervating urinary bladder in control and spinal cord injured rats.
2003,
Pubmed
Bostock,
The spatial distribution of excitability and membrane current in normal and demyelinated mammalian nerve fibres.
1983,
Pubmed
Brackenbury,
Voltage-gated Na+ channels: potential for beta subunits as therapeutic targets.
2008,
Pubmed
Bulaj,
Synthetic muO-conotoxin MrVIB blocks TTX-resistant sodium channel NaV1.8 and has a long-lasting analgesic activity.
2006,
Pubmed
Caldwell,
Sodium channel Na(v)1.6 is localized at nodes of ranvier, dendrites, and synapses.
2000,
Pubmed
Catterall,
International Union of Pharmacology. XLVII. Nomenclature and structure-function relationships of voltage-gated sodium channels.
2005,
Pubmed
Catterall,
From ionic currents to molecular mechanisms: the structure and function of voltage-gated sodium channels.
2000,
Pubmed
Cestèle,
Molecular mechanisms of neurotoxin action on voltage-gated sodium channels.
2000,
Pubmed
Chahine,
Extrapore residues of the S5-S6 loop of domain 2 of the voltage-gated skeletal muscle sodium channel (rSkM1) contribute to the mu-conotoxin GIIIA binding site.
1998,
Pubmed
,
Xenbase
Cruz,
Conus geographus toxins that discriminate between neuronal and muscle sodium channels.
1985,
Pubmed
Cummins,
Critical molecular determinants of voltage-gated sodium channel sensitivity to mu-conotoxins GIIIA/B.
2002,
Pubmed
Cummins,
The roles of sodium channels in nociception: Implications for mechanisms of pain.
2007,
Pubmed
Daly,
Structures of muO-conotoxins from Conus marmoreus. I nhibitors of tetrodotoxin (TTX)-sensitive and TTX-resistant sodium channels in mammalian sensory neurons.
2004,
Pubmed
Dib-Hajj,
NaN, a novel voltage-gated Na channel, is expressed preferentially in peripheral sensory neurons and down-regulated after axotomy.
1998,
Pubmed
Djouhri,
Sensory and electrophysiological properties of guinea-pig sensory neurones expressing Nav 1.7 (PN1) Na+ channel alpha subunit protein.
2003,
Pubmed
Ekberg,
muO-conotoxin MrVIB selectively blocks Nav1.8 sensory neuron specific sodium channels and chronic pain behavior without motor deficits.
2006,
Pubmed
,
Xenbase
Gold,
Redistribution of Na(V)1.8 in uninjured axons enables neuropathic pain.
2003,
Pubmed
Goldin,
Resurgence of sodium channel research.
2001,
Pubmed
HODGKIN,
A quantitative description of membrane current and its application to conduction and excitation in nerve.
1952,
Pubmed
Hille,
Pharmacological modifications of the sodium channels of frog nerve.
1968,
Pubmed
Holford,
Pruning nature: Biodiversity-derived discovery of novel sodium channel blocking conotoxins from Conus bullatus.
2009,
Pubmed
,
Xenbase
Isom,
Sodium channel beta subunits: anything but auxiliary.
2001,
Pubmed
Isom,
Beta subunits: players in neuronal hyperexcitability?
2002,
Pubmed
Kao,
Actions of saxitoxin on peripheral neuromuscular systems.
1965,
Pubmed
Lewis,
Isolation and structure-activity of mu-conotoxin TIIIA, a potent inhibitor of tetrodotoxin-sensitive voltage-gated sodium channels.
2007,
Pubmed
,
Xenbase
Li,
Molecular basis of isoform-specific micro-conotoxin block of cardiac, skeletal muscle, and brain Na+ channels.
2003,
Pubmed
Moczydlowski,
Discrimination of muscle and neuronal Na-channel subtypes by binding competition between [3H]saxitoxin and mu-conotoxins.
1986,
Pubmed
NARAHASHI,
TETRODOTOXIN BLOCKAGE OF SODIUM CONDUCTANCE INCREASE IN LOBSTER GIANT AXONS.
1964,
Pubmed
Raymond,
Effects of nerve impulses on threshold of frog sciatic nerve fibres.
1979,
Pubmed
Rush,
Multiple sodium channels and their roles in electrogenesis within dorsal root ganglion neurons.
2007,
Pubmed
Safo,
Distinction among neuronal subtypes of voltage-activated sodium channels by mu-conotoxin PIIIA.
2000,
Pubmed
,
Xenbase
Satin,
A mutant of TTX-resistant cardiac sodium channels with TTX-sensitive properties.
1992,
Pubmed
,
Xenbase
Schmalhofer,
ProTx-II, a selective inhibitor of NaV1.7 sodium channels, blocks action potential propagation in nociceptors.
2008,
Pubmed
Shon,
mu-Conotoxin PIIIA, a new peptide for discriminating among tetrodotoxin-sensitive Na channel subtypes.
1998,
Pubmed
Terlau,
Conus venoms: a rich source of novel ion channel-targeted peptides.
2004,
Pubmed
Tzoumaka,
Differential distribution of the tetrodotoxin-sensitive rPN4/NaCh6/Scn8a sodium channel in the nervous system.
2000,
Pubmed
Walewska,
NMR-based mapping of disulfide bridges in cysteine-rich peptides: application to the mu-conotoxin SxIIIA.
2008,
Pubmed
West,
Mu-conotoxin SmIIIA, a potent inhibitor of tetrodotoxin-resistant sodium channels in amphibian sympathetic and sensory neurons.
2002,
Pubmed
Yao,
Structure, dynamics, and selectivity of the sodium channel blocker mu-conotoxin SIIIA.
2008,
Pubmed
,
Xenbase
Zhang,
Structural and functional diversities among mu-conotoxins targeting TTX-resistant sodium channels.
2006,
Pubmed
Zhang,
Structure/function characterization of micro-conotoxin KIIIA, an analgesic, nearly irreversible blocker of mammalian neuronal sodium channels.
2007,
Pubmed
,
Xenbase
Zhang,
Synergistic and antagonistic interactions between tetrodotoxin and mu-conotoxin in blocking voltage-gated sodium channels.
2009,
Pubmed
,
Xenbase
Zhang,
μ-conotoxin KIIIA derivatives with divergent affinities versus efficacies in blocking voltage-gated sodium channels.
2010,
Pubmed
,
Xenbase
Zhang,
Cooccupancy of the outer vestibule of voltage-gated sodium channels by micro-conotoxin KIIIA and saxitoxin or tetrodotoxin.
2010,
Pubmed
,
Xenbase
