Nomenclature of Voltage-Gated Sodium Channels

Goldin, Alan L.; Barchi, Robert L.; Caldwell, John H.; Hofmann, Franz; Howe, James R.; Hunter, John C.; Kallen, Roland G.; Mandel, Gail; Meisler, Miriam H.; Netter, Yoheved Berwald; Noda, Masahara; Tamkun, Michael M.; Waxman, S. G.; Wood, John N.; Catterall, William A.

doi:10.1016/s0896-6273(00)00116-1

Cited by 951 publications

(515 citation statements)

References 6 publications

(7 reference statements)

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“…TTX pretreatment produced a concentration-dependent inhibition of ATX-induced sodium influx in rNa v 1.2-CHL 1610, rNa v 1.4-HEK 293 and rNa v 1.5-CHL 1610 cells with IC 50 values of 14.8 nM (11.2-19.8, 95% CI), 25.2 nM (20.1-31.7 nM, 95% CI) and 3.47 μM (2.33-5.15, 95% CI), respectively (Figure 5). These inhibitory potencies of TTX are consistent with the expected sodium channel pharmacology in that rNa v 1.2 and rNa v 1.4 are TTX sensitive with IC 50 values in the nanomolar range whereas rNa v 1.5 is relatively insensitive with an IC 50 value in the low micromolar range [18]. …”

Section: Resultssupporting

confidence: 76%

Antillatoxin is a sodium channel activator that displays unique efficacy in heterologously expressed rNav1.2, rNav1.4 and rNav1.5 alpha subunits

2010

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BackgroundAntillatoxin (ATX) is a structurally unique lipopeptide produced by the marine cyanobacterium Lyngbya majuscula. ATX activates voltage-gated sodium channel α-subunits at an undefined recognition site and stimulates sodium influx in neurons. However, the pharmacological properties and selectivity of ATX on the sodium channel α-subunits were not fully characterized.ResultsIn this study, we characterized the pharmacological properties and selectivity of ATX in cells heterologously expressing rNav1.2, rNav1.4 or rNav1.5 α-subunits by using the Na+ selective fluorescent dye, sodium-binding benzofuran isophthalate. ATX produced sodium influx in cells expressing each sodium channel α-subunit, whereas two other sodium channel activators, veratridine and brevetoxin-2, were without effect. The ATX potency at rNav1.2, rNav1.4 and rNav1.5 did not differ significantly. Similarly, there were no significant differences in the efficacy for ATX-induced sodium influx between rNav1.2, rNav1.4 and rNav1.5 α-subunits. ATX also produced robust Ca2+ influx relative to other sodium channel activators in the calcium-permeable DEAA mutant of rNav1.4 α-subunit. Finally, we demonstrated that the 8-demethyl-8,9-dihydro-antillatoxin analog was less efficacious and less potent in stimulating sodium influx.ConclusionsATX displayed a unique efficacy with respect to stimulation of sodium influx in cells expressing rNav1.2, rNav1.4 and rNav1.5 α-subunits. The efficacy of ATX was distinctive inasmuch as it was not shared by activators of neurotoxin sites 2 and 5 on VGSC α-subunits. Given the unique pharmacological properties of ATX interaction with sodium channel α-subunits, decoding the molecular determinants and mechanism of action of antillatoxin may provide further insight into sodium channel gating mechanisms.

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Section: Resultssupporting

confidence: 76%

Antillatoxin is a sodium channel activator that displays unique efficacy in heterologously expressed rNav1.2, rNav1.4 and rNav1.5 alpha subunits

2010

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“…KishinoHasegawa and Shimodaira-Hasegawa tests using RELL bootstraps with 1000 replicates found our topology to be significantly better at explaining the data than all three possible resolutions of Piontkivska and Hughes (2003) (Table 3), and the K-H tests also found our topology to be significantly better than Goldin et al (2000). However, the molecular data could not reject the topology of Plummer and Meisler (1999) and Goldin (2002) or the topology of Lopreato et al (2001) (Table 3).…”

Section: Tree Comparisonsmentioning

confidence: 71%

“…On the basis of several criteria and tests, our topology for mammalian SCNA gene phylogeny was significantly better at explaining the molecular data than the topology of Goldin et al (2000) and all three possible resolutions of Piontkivska and Hughes (2003) (Table 3).…”

Section: Tree Comparisonsmentioning

confidence: 97%

“…1;Plummer and Meisler 1999;Goldin et al 2000;Lopreato et al 2001;Goldin 2002;Piontkivska and Hughes 2003). Because the topology of mammalian SCNA phylogeny from Goldin (2002) is identical to that from Plummer and Meisler (1999), these two trees were treated as a single hypothesis.…”

Section: Tree Comparisonsmentioning

confidence: 99%

“…Phylogenetic analysis has been previously applied to SCNA genes to determine the evolutionary history of the vertebrate SCNA gene family (Goldin 2002;Goldin et al 2000;Lopreato et al 2001;Piontkivska and Hughes 2003;Plummer and Meisler 1999).…”

Section: Introductionmentioning

confidence: 99%

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Gene Duplications and Evolution of Vertebrate Voltage-Gated Sodium Channels

Novak¹,

Jost

et al. 2006

J Mol Evol

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Abstract.Voltage-gated sodium channels underlie action potential generation in excitable tissue.To establish the evolutionary mechanisms that shaped the vertebrate sodium channel a-subunit (SCNA) gene family and their encoded Na v 1 proteins, we identified all SCNA genes in several teleost species. Molecular cloning revealed that teleosts have eight SCNA genes, comparable to the number in another vertebrate lineage, mammals.Prior phylogenetic analyses had indicated that teleosts and tetrapods share four monophyletic groups of SCNA genes and that tandem duplications selectively expanded the number of genes in two of the four mammalian groups. However, the number of genes in each group varies between teleosts and tetrapods suggesting different evolutionary histories in the two vertebrate lineages. Our findings from phylogenetic analysis and chromosomal mapping of Danio rerio genes indicate that tandem duplications are an unlikely mechanism for generation of the extant teleost SCNA genes. Instead, analysis of other closely mapped genes in D. rerio supports the hypothesis that a whole genome duplication was involved in expansion of the SCNA gene family in teleosts. Interestingly, despite their different evolutionary histories, mRNA analyses demonstrated a conservation of expression patterns for SCNA orthologues in teleosts and tetrapods, suggesting functional conservation.

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Ion Channels and Neuronal Dysfunction in Multiple Sclerosis

Waxman¹

2002

Arch Neurol

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W hat causes the signs and symptoms of multiple sclerosis (MS)? It is almost axiomatic to regard MS as a demyelinating disorder in which axonal conduction block, caused by loss of myelin, produces clinical deficits. In addition, during the past few years, increased attention has focused on axonal degeneration in MS. The available evidence suggests that demyelination provides a structural correlate for relapsingremitting disease while axonal degeneration, which may be associated with atrophy of the brain and spinal cord, produces nonremitting deficits.

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Nomenclature of Voltage-Gated Sodium Channels

Cited by 951 publications

References 6 publications

Antillatoxin is a sodium channel activator that displays unique efficacy in heterologously expressed rNav1.2, rNav1.4 and rNav1.5 alpha subunits

Antillatoxin is a sodium channel activator that displays unique efficacy in heterologously expressed rNav1.2, rNav1.4 and rNav1.5 alpha subunits

Gene Duplications and Evolution of Vertebrate Voltage-Gated Sodium Channels

Ion Channels and Neuronal Dysfunction in Multiple Sclerosis

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