Experts and Doctors on sodium channels in Connecticut, United States

Summary

Locale: Connecticut, United States
Topic: sodium channels

Top Publications

  1. Hudmon A, Choi J, Tyrrell L, Black J, Rush A, Waxman S, et al. Phosphorylation of sodium channel Na(v)1.8 by p38 mitogen-activated protein kinase increases current density in dorsal root ganglion neurons. J Neurosci. 2008;28:3190-201 pubmed publisher
    ..Our study suggests a mechanism by which activated p38 contributes to inflammatory, and possibly neuropathic, pain through a p38-mediated increase of Na(v)1.8 current density. ..
  2. Zhang P, Canessa C. Single-channel properties of recombinant acid-sensitive ion channels formed by the subunits ASIC2 and ASIC3 from dorsal root ganglion neurons expressed in Xenopus oocytes. J Gen Physiol. 2001;117:563-72 pubmed
    ..Increasing [H(+)](o) increases the frequency of entering the modes with high P(o) (modes 1, 2, and 4) and the time the channel spends in the modes with high activity. ..
  3. Li T, Yang Y, Canessa C. Outlines of the pore in open and closed conformations describe the gating mechanism of ASIC1. Nat Commun. 2011;2:399 pubmed publisher
  4. Blumenfeld H, Klein J, Schridde U, Vestal M, Rice T, Khera D, et al. Early treatment suppresses the development of spike-wave epilepsy in a rat model. Epilepsia. 2008;49:400-9 pubmed
    ..If confirmed with other drugs and epilepsy paradigms, the availability of a model in which epileptogenesis can be controlled has important implications both for future basic studies, and human therapeutic trials. ..
  5. Vasylyev D, Waxman S. Membrane properties and electrogenesis in the distal axons of small dorsal root ganglion neurons in vitro. J Neurophysiol. 2012;108:729-40 pubmed publisher
    ..These results provide direct evidence for the presence of TTX-S and TTX-R Na(+) channels that are functionally available at resting potential and contribute to electrogenesis in small-diameter afferent axons. ..
  6. Blumenfeld H. From molecules to networks: cortical/subcortical interactions in the pathophysiology of idiopathic generalized epilepsy. Epilepsia. 2003;44 Suppl 2:7-15 pubmed
    ..A greater understanding of these molecular and network mechanisms will ultimately lead to improved targeted therapies for generalized epilepsy. ..
  7. Stys P, Waxman S, Ransom B. Ionic mechanisms of anoxic injury in mammalian CNS white matter: role of Na+ channels and Na(+)-Ca2+ exchanger. J Neurosci. 1992;12:430-9 pubmed
    ..These observations emphasize that differences in the pathophysiology of gray and white matter anoxic injury are likely to necessitate multiple strategies for optimal CNS protection. ..
  8. Gasser A, Ho T, Cheng X, Chang K, Waxman S, Rasband M, et al. An ankyrinG-binding motif is necessary and sufficient for targeting Nav1.6 sodium channels to axon initial segments and nodes of Ranvier. J Neurosci. 2012;32:7232-43 pubmed publisher
    ..Thus, the ankyrinG-binding motif is both necessary and sufficient for the clustering of sodium channels at nodes of Ranvier and the AIS. ..
  9. Berghs S, Aggujaro D, Dirkx R, Maksimova E, Stabach P, Hermel J, et al. betaIV spectrin, a new spectrin localized at axon initial segments and nodes of ranvier in the central and peripheral nervous system. J Cell Biol. 2000;151:985-1002 pubmed
    ..Thus, we suggest that betaIVSigma1 spectrin interacts with ankyrin(G) 480/270-kD and participates in the clustering of voltage-gated Na(+) channels and cell-adhesion molecules at initial segments and nodes of Ranvier. ..

More Information

Publications55

  1. Alvarez de la Rosa D, Canessa C, Fyfe G, Zhang P. Structure and regulation of amiloride-sensitive sodium channels. Annu Rev Physiol. 2000;62:573-94 pubmed
    ..Here, we review progress made during the last years in the characterization, regulation, and cloning of new amiloride-sensitive Na+ channels. ..
  2. Liu C, Dib Hajj S, Renganathan M, Cummins T, Waxman S. Modulation of the cardiac sodium channel Nav1.5 by fibroblast growth factor homologous factor 1B. J Biol Chem. 2003;278:1029-36 pubmed
    ..5 channel with FHF1B. This is the first report showing that interaction with a growth factor can modulate properties of a voltage-gated sodium channel. ..
  3. Wu M, Zaborszky L, Hajszan T, van den Pol A, Alreja M. Hypocretin/orexin innervation and excitation of identified septohippocampal cholinergic neurons. J Neurosci. 2004;24:3527-36 pubmed
    ..Thus Hcrt effects within the septum should increase hippocampal acetylcholine release and thereby promote hippocampal arousal. ..
  4. Xia Y, Zhao P, Xue J, Gu X, Sun X, Yao H, et al. Na+ channel expression and neuronal function in the Na+/H+ exchanger 1 null mutant mouse. J Neurophysiol. 2003;89:229-36 pubmed
    ..We speculate that neuronal overexcitability due to Na(+) channel upregulation in the hippocampus and cortex forms the basis of epileptic seizures in NHE1 mutant mice. ..
  5. Coric T, Zhang P, Todorovic N, Canessa C. The extracellular domain determines the kinetics of desensitization in acid-sensitive ion channel 1. J Biol Chem. 2003;278:45240-7 pubmed
    ..Functional studies of chimeras made from rat and fish ASIC1 indicate that the extracellular domain specifically, a cluster of three residues, confers the faster desensitization rate to the fish ASIC1. ..
  6. Black J, Liu S, Waxman S. Sodium channel activity modulates multiple functions in microglia. Glia. 2009;57:1072-81 pubmed publisher
    ..6) indicate that Nav1.6 plays a role in microglial migration. The results demonstrate that the activity of sodium channels contributes to effector roles of activated microglia. ..
  7. Fischer T, Waxman S. Familial pain syndromes from mutations of the NaV1.7 sodium channel. Ann N Y Acad Sci. 2010;1184:196-207 pubmed publisher
    ..7 channel may provide a unique target for the pharmacotherapy of pain in humans. In this review article we summarize current knowledge regarding several different disease manifestations arising from changes within the Na(v)1.7 channel. ..
  8. Sanders S, Murtha M, Gupta A, Murdoch J, Raubeson M, Willsey A, et al. De novo mutations revealed by whole-exome sequencing are strongly associated with autism. Nature. 2012;485:237-41 pubmed publisher
  9. Ho T, Zollinger D, Chang K, Xu M, Cooper E, Stankewich M, et al. A hierarchy of ankyrin-spectrin complexes clusters sodium channels at nodes of Ranvier. Nat Neurosci. 2014;17:1664-72 pubmed publisher
  10. Hansson J, Nelson Williams C, Suzuki H, Schild L, Shimkets R, Lu Y, et al. Hypertension caused by a truncated epithelial sodium channel gamma subunit: genetic heterogeneity of Liddle syndrome. Nat Genet. 1995;11:76-82 pubmed
  11. Alvarez de la Rosa D, Krueger S, Kolar A, Shao D, Fitzsimonds R, Canessa C. Distribution, subcellular localization and ontogeny of ASIC1 in the mammalian central nervous system. J Physiol. 2003;546:77-87 pubmed
  12. Nelson J, Wyman R. Examination of paralysis in Drosophila temperature-sensitive paralytic mutations affecting sodium channels; a proposed mechanism of paralysis. J Neurobiol. 1990;21:453-69 pubmed
    ..These two reductions in sodium current combine to prevent spiking threshold from being reached at current limited sites. The temperature at which a sufficient number of these sites block should be the temperature of paralysis. ..
  13. Trimmer J, Cooperman S, Tomiko S, Zhou J, Crean S, Boyle M, et al. Primary structure and functional expression of a mammalian skeletal muscle sodium channel. Neuron. 1989;3:33-49 pubmed
    ..The expressed sodium channels have gating kinetics similar to the native channels in rat muscle fibers, except that inactivation occurs more slowly. ..
  14. Shimkets R, Warnock D, Bositis C, Nelson Williams C, Hansson J, Schambelan M, et al. Liddle's syndrome: heritable human hypertension caused by mutations in the beta subunit of the epithelial sodium channel. Cell. 1994;79:407-14 pubmed
    ..These findings demonstrate that Liddle's syndrome is caused by mutations in the beta subunit of the epithelial sodium channel and have implications for the regulation of this epithelial ion channel as well as blood pressure homeostasis. ..
  15. Li T, Yang Y, Canessa C. Interaction of the aromatics Tyr-72/Trp-288 in the interface of the extracellular and transmembrane domains is essential for proton gating of acid-sensing ion channels. J Biol Chem. 2009;284:4689-94 pubmed publisher
    ..We propose that such interaction may provide functional coupling between the extracellular domain and the pore domain. ..
  16. Cheng X, Dib Hajj S, Tyrrell L, Waxman S. Mutation I136V alters electrophysiological properties of the Na(v)1.7 channel in a family with onset of erythromelalgia in the second decade. Mol Pain. 2008;4:1 pubmed publisher
    ..7, compared to the other reported cases of inherited erythromelalgia, may contribute to the later age of onset and slower progression of the symptoms reported in association with this mutation. ..
  17. Harty T, Dib Hajj S, Tyrrell L, Blackman R, Hisama F, Rose J, et al. Na(V)1.7 mutant A863P in erythromelalgia: effects of altered activation and steady-state inactivation on excitability of nociceptive dorsal root ganglion neurons. J Neurosci. 2006;26:12566-75 pubmed
    ..Thus, A863P mutant channels produce hyperexcitability in DRG neurons, which contributes to the pathophysiology of IEM. ..
  18. Shah B, Rush A, Liu S, Tyrrell L, Black J, Dib Hajj S, et al. Contactin associates with sodium channel Nav1.3 in native tissues and increases channel density at the cell surface. J Neurosci. 2004;24:7387-99 pubmed
    ..We propose that the upregulation of contactin and its colocalization with Na(v)1.3 in axotomized DRG neurons may contribute to the hyper-excitablity of the injured neurons. ..
  19. Wittmack E, Rush A, Craner M, Goldfarb M, Waxman S, Dib Hajj S. Fibroblast growth factor homologous factor 2B: association with Nav1.6 and selective colocalization at nodes of Ranvier of dorsal root axons. J Neurosci. 2004;24:6765-75 pubmed
    ..The preferential expression of FHF2B in sensory neurons may provide a basis for physiological differences in sodium currents that have been reported at the nodes of Ranvier in sensory versus motor axons. ..
  20. Choi I, Aalkjaer C, Boulpaep E, Boron W. An electroneutral sodium/bicarbonate cotransporter NBCn1 and associated sodium channel. Nature. 2000;405:571-5 pubmed
    ..Oocytes injected with low levels of NBCn1-B complementary RNA exhibit a Na+ conductance that 4,4-diisothiocyanatostilbene-2,2'-disulphonate stimulates slowly and irreversibly. ..
  21. Hains B, Saab C, Klein J, Craner M, Waxman S. Altered sodium channel expression in second-order spinal sensory neurons contributes to pain after peripheral nerve injury. J Neurosci. 2004;24:4832-9 pubmed
    ..3 sodium channel and central mechanisms that contribute to neuropathic pain after peripheral nerve injury. ..
  22. Herzog R, Liu C, Waxman S, Cummins T. Calmodulin binds to the C terminus of sodium channels Nav1.4 and Nav1.6 and differentially modulates their functional properties. J Neurosci. 2003;23:8261-70 pubmed
  23. Ravindran A, Kwiecinski H, Alvarez O, Eisenman G, Moczydlowski E. Modeling ion permeation through batrachotoxin-modified Na+ channels from rat skeletal muscle with a multi-ion pore. Biophys J. 1992;61:494-508 pubmed
    ..However, if negative surface charges of the protein do influence conduction, the conductance behavior in the limit of low [Na+] does not correspond to a Gouy-Chapman model of planar surface charge. ..
  24. Casale A, McCormick D. Active action potential propagation but not initiation in thalamic interneuron dendrites. J Neurosci. 2011;31:18289-302 pubmed publisher
  25. Ravindran A, Moczydlowski E. Influence of negative surface charge on toxin binding to canine heart Na channels in planar bilayers. Biophys J. 1989;55:359-65 pubmed
    ..Thus, negative surface charge is a conserved feature of channel function of these two subtypes. The difference in toxin binding affinities arises from small differences in intrinsic association and dissociation rates. ..
  26. Gasser A, Cheng X, Gilmore E, Tyrrell L, Waxman S, Dib Hajj S. Two Nedd4-binding motifs underlie modulation of sodium channel Nav1.6 by p38 MAPK. J Biol Chem. 2010;285:26149-61 pubmed publisher
    ..6 is necessary for stress-induced current modulation, with positive or negative regulation depending upon the availability of the C-terminal Pro-Ser-Tyr motif to bind Nedd4-2. ..
  27. Li T, Yang Y, Canessa C. Two residues in the extracellular domain convert a nonfunctional ASIC1 into a proton-activated channel. Am J Physiol Cell Physiol. 2010;299:C66-73 pubmed publisher
  28. Lilly M, Kreber R, Ganetzky B, Carlson J. Evidence that the Drosophila olfactory mutant smellblind defines a novel class of sodium channel mutation. Genetics. 1994;136:1087-96 pubmed
    ..Two sbl mutations produce olfactory defects not characteristic of classic sodium channel mutations and do not show typical heat-sensitive paralysis, suggesting that these sbl mutants define a novel class of sodium channel mutation. ..
  29. Liu C, Somps C. Na+/H+ exchanger-1 inhibitors reduce neuronal excitability and alter na+ channel inactivation properties in rat primary sensory neurons. Toxicol Sci. 2008;103:346-53 pubmed publisher
    ..Such effects may underlie peripheral neuropathies reported in rats and dogs with NHE-1 inhibitors. ..
  30. Hains B, Klein J, Saab C, Craner M, Black J, Waxman S. Upregulation of sodium channel Nav1.3 and functional involvement in neuronal hyperexcitability associated with central neuropathic pain after spinal cord injury. J Neurosci. 2003;23:8881-92 pubmed
    ..3 expression and neuronal hyperexcitability associated with central neuropathic pain. ..
  31. Wittmack E, Rush A, Hudmon A, Waxman S, Dib Hajj S. Voltage-gated sodium channel Nav1.6 is modulated by p38 mitogen-activated protein kinase. J Neurosci. 2005;25:6621-30 pubmed
    ..6 current density. This is the first demonstration of MAPK phosphorylation and modulation of a voltage-gated sodium channel, and this modulation may represent an additional role for MAPK in regulating the neuronal response to injury. ..
  32. Estacion M, Dib Hajj S, Benke P, Te Morsche R, Eastman E, MacAla L, et al. NaV1.7 gain-of-function mutations as a continuum: A1632E displays physiological changes associated with erythromelalgia and paroxysmal extreme pain disorder mutations and produces symptoms of both disorders. J Neurosci. 2008;28:11079-88 pubmed publisher
    ..These observations indicate that IEM and PEPD mutants are part of a physiological continuum that can produce a continuum of clinical phenotypes. ..
  33. Shields S, Cheng X, Uceyler N, Sommer C, Dib Hajj S, Waxman S. Sodium channel Na(v)1.7 is essential for lowering heat pain threshold after burn injury. J Neurosci. 2012;32:10819-32 pubmed publisher
    ..Our results offer insights into the molecular and cellular mechanisms of modality-specific pain signaling, and suggest Na(v)1.7-blocking drugs may be effective in burn patients. ..
  34. Carrithers M, Chatterjee G, Carrithers L, Offoha R, Iheagwara U, Rahner C, et al. Regulation of podosome formation in macrophages by a splice variant of the sodium channel SCN8A. J Biol Chem. 2009;284:8114-26 pubmed publisher
    ..6 participates in the control of podosome and invadopodia formation and suggest that intracellular sodium release mediated by NaV1.6 may regulate cellular invasion of macrophages and melanoma cells. ..
  35. Gu X, Yao H, Haddad G. Increased neuronal excitability and seizures in the Na(+)/H(+) exchanger null mutant mouse. Am J Physiol Cell Physiol. 2001;281:C496-503 pubmed
    ..We hypothesize that the increased neuronal excitability and possibly the seizure disorder in mice lacking the NHE1 is due, at least in part, to changes in Na(+) channel expression and/or regulation...
  36. Lampert A, Dib Hajj S, Tyrrell L, Waxman S. Size matters: Erythromelalgia mutation S241T in Nav1.7 alters channel gating. J Biol Chem. 2006;281:36029-35 pubmed
    ..We conclude that the linker between S4 and S5 in domain I of Nav1.7 modulates gating of this channel, and that a larger side chain at position 241 interferes with its gating mechanisms. ..
  37. Hains B, Saab C, Waxman S. Alterations in burst firing of thalamic VPL neurons and reversal by Na(v)1.3 antisense after spinal cord injury. J Neurophysiol. 2006;95:3343-52 pubmed
    ..These results demonstrate several newly characterized changes in spontaneous burst firing properties of VPL neurons after SCI and suggest that abnormal expression of Na(v)1.3 contributes to these phenomena. ..
  38. Li T, Yang Y, Canessa C. Asn415 in the beta11-beta12 linker decreases proton-dependent desensitization of ASIC1. J Biol Chem. 2010;285:31285-91 pubmed publisher
    ..Substitutions of Asn-415 for Cys, Ser, or Gly render ASIC1 responsive to small increases in proton concentrations near the baseline physiological pH. ..
  39. Craner M, Kataoka Y, Lo A, Black J, Baker D, Waxman S. Temporal course of upregulation of Na(v)1.8 in Purkinje neurons parallels the progression of clinical deficit in experimental allergic encephalomyelitis. J Neuropathol Exp Neurol. 2003;62:968-75 pubmed
    ..8 expression. These results provide evidence that the expression of sodium channel Na(v)1.8 contributes to the development of clinical deficits in an in vivo model of neuroinflammatory disease...
  40. Stephan M, Agnew W. Voltage-sensitive Na+ channels: motifs, modes and modulation. Curr Opin Cell Biol. 1991;3:676-84 pubmed
    ..At the same time, however, electrophysiological studies have revealed new, more complex functional properties in the form of at least two gating modes and the existence of as yet unidentified modulatory factors. ..
  41. Dib Hajj S, Tyrrell L, Escayg A, Wood P, Meisler M, Waxman S. Coding sequence, genomic organization, and conserved chromosomal localization of the mouse gene Scn11a encoding the sodium channel NaN. Genomics. 1999;59:309-18 pubmed
    ..The human gene, SCN11A, was mapped to the conserved linkage group on chromosome 3p21-p24, close to human SCN5A and SCN10A. The colocalization of the three sodium channel genes supports a common lineage of the TTX-R sodium channels. ..
  42. Liu Cj -, Dib Hajj S, Waxman S. Fibroblast growth factor homologous factor 1B binds to the C terminus of the tetrodotoxin-resistant sodium channel rNav1.9a (NaN). J Biol Chem. 2001;276:18925-33 pubmed
    ..9a channel directly or by recruiting other proteins to the channel complex. Alternatively, it is possible that rNa(v)1.9a may help deliver this factor to the cell membrane, where it exerts its function. ..
  43. Stamboulian S, Choi J, Ahn H, Chang Y, Tyrrell L, Black J, et al. ERK1/2 mitogen-activated protein kinase phosphorylates sodium channel Na(v)1.7 and alters its gating properties. J Neurosci. 2010;30:1637-47 pubmed publisher
    ..7 by pERK1/2, which unlike the modulation of Na(v)1.6 and Na(v)1.8 by pp38, regulates gating properties of this channel but not its current density and contributes to the effects of MAPKs on DRG neuron excitability. ..
  44. Klein J, Tendi E, Dib Hajj S, Fields R, Waxman S. Patterned electrical activity modulates sodium channel expression in sensory neurons. J Neurosci Res. 2003;74:192-8 pubmed
    ..These results show that a change in neuronal activity can alter the expression of sodium channel genes in a subtype-specific manner, via a mechanism independent of NGF withdrawal. ..
  45. Lilly M, Riesgo Escovar J, Carlson J. Developmental analysis of the smellblind mutants: evidence for the role of sodium channels in Drosophila development. Dev Biol. 1994;162:1-8 pubmed
    ..These results are discussed in terms of the developmental role of the para sodium channel and the role of electrical activity in Drosophila development. ..
  46. Jarecki J, Keshishian H. Role of neural activity during synaptogenesis in Drosophila. J Neurosci. 1995;15:8177-90 pubmed
    ..Our experiments suggest that neural activity may function during development by preventing inappropriate connections and thereby maintaining the precise connectivity achieved during nerve outgrowth and target selection. ..