Click here to close
Hello! We notice that you are using Internet Explorer, which is not supported by Xenbase and may cause the site to display incorrectly.
We suggest using a current version of Chrome,
FireFox, or Safari.
Α- and β-subunit composition of voltage-gated sodium channels investigated with μ-conotoxins and the recently discovered μO§-conotoxin GVIIJ.
Wilson MJ
,
Zhang MM
,
Gajewiak J
,
Azam L
,
Rivier JE
,
Olivera BM
,
Yoshikami D
.
???displayArticle.abstract???
We investigated the identities of the isoforms of the α (NaV1)- and β (NaVβ)-subunits of voltage-gated sodium channels, including those responsible for action potentials in rodent sciatic nerves. To examine α-subunits, we used seven μ-conotoxins, which target site 1 of the channel. With the use of exogenously expressed channels, we show that two of the μ-conotoxins, μ-BuIIIB and μ-SxIIIA, are 50-fold more potent in blocking NaV1.6 from mouse than that from rat. Furthermore, we observed that μ-BuIIIB and μ-SxIIIA are potent blockers of large, myelinated A-fiber compound action potentials (A-CAPs) [but not small, unmyelinated C-fiber CAPs (C-CAPs)] in the sciatic nerve of the mouse (unlike A-CAPs of the rat, previously shown to be insensitive to these toxins). To investigate β-subunits, we used two synthetic derivatives of the recently discovered μO§-conotoxin GVIIJ that define site 8 of the channel, as previously characterized with cloned rat NaV1- and NaVβ-subunits expressed in Xenopus laevis oocytes, where it was shown that μO§-GVIIJ is a potent inhibitor of several NaV1-isoforms and that coexpression of NaVβ2 or -β4 (but not NaVβ1 or -β3) totally protects against block by μO§-GVIIJ. We report here the effects of μO§-GVIIJ on 1) sodium currents of mouse NaV1.6 coexpressed with various combinations of NaVβ-subunits in oocytes; 2) A- and C-CAPs of mouse and rat sciatic nerves; and 3) sodium currents of small and large neurons dissociated from rat dorsal root ganglia. Our overall results lead us to conclude that action potentials in A-fibers of the rodent sciatic nerve are mediated primarily by NaV1.6 associated with NaVβ2 or NaVβ4.
Bant,
Control of transient, resurgent, and persistent current by open-channel block by Na channel beta4 in cultured cerebellar granule neurons.
2010, Pubmed
Bant,
Control of transient, resurgent, and persistent current by open-channel block by Na channel beta4 in cultured cerebellar granule neurons.
2010,
Pubmed
Blair,
Roles of tetrodotoxin (TTX)-sensitive Na+ current, TTX-resistant Na+ current, and Ca2+ current in the action potentials of nociceptive sensory neurons.
2002,
Pubmed
Buffington,
Na+ channel-dependent recruitment of Navβ4 to axon initial segments and nodes of Ranvier.
2013,
Pubmed
Bulaj,
Synthetic muO-conotoxin MrVIB blocks TTX-resistant sodium channel NaV1.8 and has a long-lasting analgesic activity.
2006,
Pubmed
Bulaj,
Delta-conotoxin structure/function through a cladistic analysis.
2001,
Pubmed
Calhoun,
The role of non-pore-forming β subunits in physiology and pathophysiology of voltage-gated sodium channels.
2014,
Pubmed
Cartier,
A new alpha-conotoxin which targets alpha3beta2 nicotinic acetylcholine receptors.
1996,
Pubmed
,
Xenbase
Catterall,
Structure and function of voltage-gated sodium channels at atomic resolution.
2014,
Pubmed
Catterall,
Voltage-gated sodium channels at 60: structure, function and pathophysiology.
2012,
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
Chen,
Identification of the cysteine residue responsible for disulfide linkage of Na+ channel α and β2 subunits.
2012,
Pubmed
Choi,
Calmodulin regulates current density and frequency-dependent inhibition of sodium channel Nav1.8 in DRG neurons.
2006,
Pubmed
Colquhoun,
The interaction at equilibrium between tetrodotoxin and mammalian non-myelinated nerve fibres.
1972,
Pubmed
Coward,
Sodium channel beta1 and beta2 subunits parallel SNS/PN3 alpha-subunit changes in injured human sensory neurons.
2001,
Pubmed
Cruz,
Conus geographus toxins that discriminate between neuronal and muscle sodium channels.
1985,
Pubmed
Cummins,
Nav1.6 channels generate resurgent sodium currents in spinal sensory neurons.
2005,
Pubmed
Dietrich,
Functional analysis of a voltage-gated sodium channel and its splice variant from rat dorsal root ganglia.
1998,
Pubmed
,
Xenbase
Fern,
The variation in safety factor with myelinated axon diameter: experiments with low sodium perfusion.
1993,
Pubmed
Fiedler,
Specificity, affinity and efficacy of iota-conotoxin RXIA, an agonist of voltage-gated sodium channels Na(V)1.2, 1.6 and 1.7.
2008,
Pubmed
,
Xenbase
Gajewiak,
A disulfide tether stabilizes the block of sodium channels by the conotoxin μO§-GVIIJ.
2014,
Pubmed
Gilchrist,
Crystallographic insights into sodium-channel modulation by the β4 subunit.
2013,
Pubmed
,
Xenbase
Grieco,
Open-channel block by the cytoplasmic tail of sodium channel beta4 as a mechanism for resurgent sodium current.
2005,
Pubmed
Harper,
Conduction velocity is related to morphological cell type in rat dorsal root ganglion neurones.
1985,
Pubmed
He,
Functional expression of Rat Nav1.6 voltage-gated sodium channels in HEK293 cells: modulation by the auxiliary β1 subunit.
2014,
Pubmed
,
Xenbase
Heinemann,
Conotoxins of the O-superfamily affecting voltage-gated sodium channels.
2007,
Pubmed
Ho,
Differential expression of sodium channel β subunits in dorsal root ganglion sensory neurons.
2012,
Pubmed
Laedermann,
β1- and β3- voltage-gated sodium channel subunits modulate cell surface expression and glycosylation of Nav1.7 in HEK293 cells.
2013,
Pubmed
Leipold,
muO conotoxins inhibit NaV channels by interfering with their voltage sensors in domain-2.
2007,
Pubmed
Leipold,
Molecular determinants for the subtype specificity of μ-conotoxin SIIIA targeting neuronal voltage-gated sodium channels.
2011,
Pubmed
Leipold,
Molecular interaction of delta-conotoxins with voltage-gated sodium channels.
2005,
Pubmed
Lewis,
Resurgent current of voltage-gated Na(+) channels.
2014,
Pubmed
Li,
Molecular basis of isoform-specific micro-conotoxin block of cardiac, skeletal muscle, and brain Na+ channels.
2003,
Pubmed
Raman,
Altered subthreshold sodium currents and disrupted firing patterns in Purkinje neurons of Scn8a mutant mice.
1997,
Pubmed
Raman,
Resurgent sodium current and action potential formation in dissociated cerebellar Purkinje neurons.
1997,
Pubmed
Santarelli,
A cation-pi interaction discriminates among sodium channels that are either sensitive or resistant to tetrodotoxin block.
2007,
Pubmed
,
Xenbase
Stevens,
Neurotoxins and their binding areas on voltage-gated sodium channels.
2011,
Pubmed
Takahashi,
Expression of auxiliary beta subunits of sodium channels in primary afferent neurons and the effect of nerve injury.
2003,
Pubmed
Tan,
Independent and joint modulation of rat Nav1.6 voltage-gated sodium channels by coexpression with the auxiliary β1 and β2 subunits.
2011,
Pubmed
,
Xenbase
Tan,
Coexpression with Auxiliary β Subunits Modulates the Action of Tefluthrin on Rat Na(v)1.6 and Na(v)1.3 Sodium Channels.
2011,
Pubmed
,
Xenbase
West,
Effects of delta-conotoxins PVIA and SVIE on sodium channels in the amphibian sympathetic nervous system.
2005,
Pubmed
Wicher,
Sensory receptors-design principles revisited.
2013,
Pubmed
Wilson,
Navβ subunits modulate the inhibition of Nav1.8 by the analgesic gating modifier μO-conotoxin MrVIB.
2011,
Pubmed
,
Xenbase
Wilson,
μ-Conotoxins that differentially block sodium channels NaV1.1 through 1.8 identify those responsible for action potentials in sciatic nerve.
2011,
Pubmed
,
Xenbase
Yan,
FGF14 modulates resurgent sodium current in mouse cerebellar Purkinje neurons.
2014,
Pubmed
Yu,
Sodium channel beta4, a new disulfide-linked auxiliary subunit with similarity to beta2.
2003,
Pubmed
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
Zhang,
Co-expression of Na(V)β subunits alters the kinetics of inhibition of voltage-gated sodium channels by pore-blocking μ-conotoxins.
2013,
Pubmed
,
Xenbase
Zhang,
Synergistic and antagonistic interactions between tetrodotoxin and mu-conotoxin in blocking voltage-gated sodium channels.
2009,
Pubmed
,
Xenbase
Zhang,
Pharmacological fractionation of tetrodotoxin-sensitive sodium currents in rat dorsal root ganglion neurons by μ-conotoxins.
2013,
Pubmed
,
Xenbase
