Abstract
Voltage-gated sodium channels (VGSCs) are vital for the normal functioning of most excitable cells. At least nine distinct functional subtypes of VGSCs are recognized, corresponding to nine genes for their pore-forming α-subunits. These have different developmental expression patterns, different tissue distributions in the adult and are differentially regulated at the cellular level by receptor-coupled cell signalling systems. Unsurprisingly, VGSC blockers are found to be useful as drugs in diverse clinical applications where excessive excitability of tissue leads to pathological dysfunction, e.g. epilepsy or cardiac tachyarrhythmias. The effects of most clinically useful VGSC blockers are use-dependent, i.e. their efficacy depends on channel activity. In addition, many natural toxins have been discovered that interact with VGSCs in complex ways and they have been used as experimental probes to study the structure and function of the channels and to better understand how drugs interact with the channels. Here we have attempted to summarize the properties of VGSCs in sensory neurones, discuss how they are regulated by cell signalling systems and we have considered briefly current concepts of their physiological function. We discuss in detail how drugs and toxins interact with archetypal VGSCs and where possible consider how they act on VGSCs in peripheral sensory neurones. Increasingly, drugs that block VGSCs are being used as systemic analgesic agents in chronic pain syndromes, but the full potential for VGSC blockers in this indication is yet to be realized and other applications in sensory dysfunction are also possible. Drugs targeting VGSC subtypes in sensory neurones are likely to provide novel systemic analgesics that are tissue-specific and perhaps even disease-specific, providing much-needed novel therapeutic approaches for the relief of chronic pain.
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- BTX:
-
Batrachotoxin
- DRG:
-
Dorsal root ganglion
- IFM:
-
Isoleucine, phenylalanine and methionine
- MAPK:
-
Mitogen-activated protein kinase
- PKA:
-
Protein kinase A
- PKC:
-
Protein kinase C
- STX:
-
Saxitoxin
- TTX:
-
Tetrodotoxin
- TTXR:
-
Tetrodotoxin resistant
- TTXS:
-
Tetrodotoxin sensitive
- VGSC:
-
Voltage-gated sodium channel
References
Ahern CA, Eastwood AL, Dougherty DA, Horn RA (2008) Electrostatic contributions of aromatic residues in the local anesthetic receptor of voltage-gated sodium channels. Circ Res 102:86–94
Akada Y, Ogawa S, Amano K, Fukudome Y, Yamasaki F, Itoh M, Yamamoto I (2006) Potent analgesic effects of a putative sodium channel blocker M58373 on formalin-induced and neuropathic pain in rats. Eur J Pharmacol 536:248–255
Alpert LA, Fozzard HA, Hanck DA, Makielski JC (1989) Is there a second external lidocaine binding site on mammalian cardiac cells? Am J Physiol 257:H79–H84
Amir R, Argoff CE, Bennett GJ, Cummins TR, Durieux ME, Gerner P, Gold MS, Porreca F, Strichartz GR (2006) The role of sodium channels in chronic inflammatory and neuropathic pain. J Pain 7(Suppl 3):S1–S29
Anger T, Madge DJ, Mulla M, Riddall D (2001) Medicinal chemistry of neuronal voltage-gated sodium channel blockers. J Med Chem 44:115–137
Armstrong CM (1971) Interaction of tetraethyammonium ion derivatives with the potassium channels of giant axons. J Gen Physiol 58:413–437
Armstrong CM (2007) Na channel inactivation from open and closed states. Proc Natl Acad Sci USA 103:17991–17996
Baker MD (2000) Selective block of late Na+ current by local anaesthetics in rat large sensory neurones. Br J Pharmacol 129:1617–1626
Baker MD (2005) Protein kinase C mediates up-regulation of tetrodotoxin-resistant, persistent Na+ current in rat and mouse sensory neurones. J Physiol 567:851–867
Balser JR, Nuss HB, Romashko DN, Marban E, Tomaselli GF (1996) Functional consequences of lidocaine binding to slow-inactivated sodium channels. J Gen Physiol 107:643–658
Becker S, Prusak-Sochaczewski E, Zamponi G, Beck-Sickinger AG, Gordon RD, French RJ (1992) Action of derivatives of mu-conotoxin GIIIA on sodium channels. Single amino acid substitutions in the toxin separately affect association and dissociation rates. Biochemistry 31:8229–8238
Benjamin ER, Pruthi F, Olanrewaju S, Ilyin VI, Crumley G, Kutlina E, Valenzano KJ, Woodward RM (2006) State-dependent compound inhibition of NaV1.2 sodium channels using the FLIPR Vm dye: on-target effects of diverse pharmacological agents. J Biomol Screen 11:29–39
Bennett PB, Valenzuela C, Chen LQ, Kallen RG (1995) On the molecular nature of the lidocaine receptor of cardiac Na+ channels. Modification of block by alterations in the alpha-subunit III–IV interdomain. Circ Res 77:584–592
Binshtok AM, Bean BP, Wolff CJ (2007) Inhibition of nociceptors by entry of impermeant sodium channel blockers. Nature 449:607–610
Black JA, Dib-Hajj S, McNabola K, Jeste S, Rizzo MA, Kocsis JD, Waxman SG (1996) Spinal sensory neurons express multiple sodium channel alpha-subunit mRNAs. Brain Res Mol Brain Res 43:117–131
Black JA, Cummins TR, Plumpton C, Chen YH, Hormuzdiar W, Clare JJ, Waxman SG (1999) Upregulation of a silent sodium channel after peripheral, but not central, nerve injury in DRG neurons. J Neurophysiol 82:2776–2785
Black JA, Renganathan M, Waxman SG (2002) Sodium channel NaV1.6 is expressed along nonmyelinated axons and it contributes to conduction. Brain Res Mol Brain Res 105:19–28
Blackburn-Munro G, Fleetwood-Walker SM (1997) The effects of Na+ channel blockers on somatosensory processing by rat dorsal horn neurones. Neuroreport 8:1549–1554
Blair NT, Bean BP (2003) Role of tetrodotoxin-resistant Na+ current slow inactivation in adaptation of action potential firing in small-diameter dorsal root ganglion neurons. J Neurosci 23:10338–10350
Bosmans F, Tytgat J (2007) Voltage-gated sodium channel modulation by scorpion alpha-toxins. Toxicon 49:142–158
Bosmans F, Maertens C, Verdonck F, Tytgat J (2004) The poison dart frog's batrachotoxin modulates NaV1.8. FEBS Lett 577:245–248
Brau ME, Elliott JR (1998) Local anaesthetic effects on tetrodotoxin-resistant Na+ currents in rat dorsal root ganglion neurons. Eur J Anaesthesiol 15:80–88
Brau ME, Dreimann M, Oischewski A, Vogel W, Hempelmann G (2001) Effect of drugs used for neuropathic pain management on tetrodotoxin-resistant Na+ currents in rat sensory neurons. Anesthesiology 94:137–144
Brochu RM, Dick IE, Tarpley JW, McGowan E, Gunner D, Herrington J, Shao PP, Ok D, Li C, Parsons WH, Stump GL, Regan CP, Lynch JJ Jr, Lyons KA, McManus OB, Clark S, Ali Z, Kaczorowski GJ, Martin WJ, Priest BT (2006) Block of peripheral nerve sodium channels selectively inhibits features of neuropathic pain in rats. Mol Pharmacol 69:823–832
Caeser M, Seabrook GR, Kemp JA (1993) Block of voltage-dependent sodium currents by the substance P receptor antagonist (+/−)-CP-96,345 in neurones cultured from rat cortex. Br J Pharmacol 109:918–924
Caldwell JH, Schaller KL, Lasher RS, Peles E, Levinson SR (2000) Sodium channel NaV1.6 is localized at nodes of Ranvier, dendrites, and synapses. Proc Natl Acad Sci USA 97:5616–5620
Cameron J, Flowers AE, Capra MF (1991) Electrophysiological studies on ciguatera poisoning in man (part II). J Neurol Sci 101:93–97
Campos FV, Moreira TH, Beirão PSL, Cruz JS (2004) Veratridine modifies the TTX-resistant Na+ channels in rat vagal afferent neurons. Toxicon 43:401–406
Campos FV, Chanda B, Beirão PS, Bezanilla F (2007) beta-Scorpion toxin modifies gating transitions in all four voltage sensors of the sodium channel. J Gen Physiol 130:257–268
Cantrell AR, Tibbs VC, Yu FH, Murphy BJ, Sharp EM, Qu Y, Catterall WA, Scheuer T (2002) Molecular mechanism of convergent regulation of brain Na+ channels by protein kinase C and protein kinase A anchored to AKAP-15. Mol Cell Neurosci 21:63–80
Cardenas LM, Cardenas CG, Scroggs RS (2001) 5HT increases excitability of nociceptor-like rat dorsal root ganglion neurons via cAMP-coupled TTX-resistant Na+ channels. J Neurophysiol 86:241–248
Cardenas CA, Cardenas CG, de Armandi AJ, Scroggs RS (2006) Carbamazepine interacts with a slow inactivation state of NaV1.8-like sodium channels. Neurosci Lett 408:129–134
Carroll I (2007) Intravenous lidocaine for neuropathic pain: diagnostic utility and therapeutic efficacy. Curr Pain Headache Rep 11:20–24
Catterall WA (1987) Common modes of drug action on Na+ channels: local anesthetics, antiarrhymics and anticonvulsants. Trends Pharmacol Sci 8:57–65
Catterall WA (1986) Voltage-dependent gating of sodium channels: correlating structure and function. Trends Neurosci 9:7–10
Catterall WA (2000) From ionic currents to molecular mechanisms: the structure and function of voltage-gated sodium channels. Neuron 26:13–25
Catterall WA, Goldin AL, Waxman SG (2005) International Union of Pharmacology. XLVII. Nomenclature and structure-function relationships of voltage-gated sodium channels. Pharmacol Rev 57:397–409
Cestele S, Catterall WA (2000) Molecular mechanisms of neurotoxin action on voltage-gated sodium channels. Biochimie 82:883–892
Chabal C, Russell LC, Burchiel KJ (1989) The effect of intravenous lidocaine, tocainide, and mexiletine on spontaneously active fibers originating in rat sciatic neuromas. Pain 38:333–338
Chahine M, Ziane R, Vijayaragavan K, Okamura Y (2005) Regulation of Na v channels in sensory neurons. Trends Pharmacol Sci 26:496–502
Challapalli V, Tremont-Lukats IW, McNicol ED, Lau J, Carr DB (2005) Systemic administration of local anesthetic agents to relieve neuropathic pain. Cochrane Database Syst Rev 4:CD003345
Chen H, Lu SQ, Leipold E, Gordon D, Hansel A, Heinemann SH (2002) Differential sensitivity of sodium channels from the central and peripheral nervous system to the scorpion toxins Lqh-2 and Lqh-3. Eur J Neurosci 16:767–770
Chen J, Tan ZY, Zhao R, Feng XH, Shi J, Ji YH (2005) The modulation effects of BmK I, an alpha-like scorpion neurotoxin on voltage-gated Na+ currents in rat dorsal root ganglion neurons. Neurosci Lett 390:66–71
Chen J, Feng XH, Shi J, Tan ZY, Bai ZT, Liu T, Ji YH (2006a) The anti-nociceptive effect of BmK AS, a scorpion active polypeptide, and the possible mechanism on specifically modulating voltage-gated Na+ currents in primary afferent neurons. Peptides 27:2182–2192
Chen Y, Yu FH, Surmeier DJ, Scheuer T, Catterall WA (2006b) Neuromodulation of Na+ channel slow inactivation via cAMP-dependent protein kinase and protein kinase C. Neuron 49:409–420
Chen D, Reierstad S, Lin Z, Lu M, Brooks C, Li N, Innes J, Bulun SE (2007) Prostaglandin E2 induces breast cancer related aromatase promoters via activation of p38 and c-Jun NH2-terminal kinase in adipose fibroblasts. Cancer Res 67:8914–8922
Cheung H, Kamp D, Harris E (1992) An in vitro investigation of the action of lamotrigine on neuronal voltage-activated sodium channels. Epilepsy Res 13(2):107–12
Chevrier P, Vijayaragavan K, Chahine M (2004) Differential modulation of NaV1.7 and NaV1.8 peripheral nerve sodium channels by the local anaesthetic lidocaine. Br J Pharmacol 142:576–584
Choi JS, Soderlund DM (2006) Structure-activity relationships for the action of 11 pyrethroid insecticides on rat Nav 1.8 sodium channels expressed in Xenopus oocytes. Toxicol Appl Pharmacol 211:233–244
Choudhary G, Yotsu-Yamashita M, Shang L, Yasumoto T, Dudley SC Jr (2003) Interactions of the C-11 hydroxyl of tetrodotoxin with the sodium channel outer vestibule. Biophys J 84:287–294
Conti F, Gheri A, Pusch M, Moran O (1996) Use dependence of tetrodotoxin block of sodium channels: a revival of the trapped-ion mechanism. Biophys J 71:1295–1312
Courtney KR (1975) Mechanism of frequency-dependent inhibition of sodium currents in from myelinated nerve by the lidocaine derivative GEA 968. J Pharm Exp Ther 195:225–236
Cox JJ, Reimann F, Nicholas AK, Thornton G, Roberts E, Springell K, Karbani G, Jafri H, Mannan J, Raashid Y, Al-Gazali L, Hamamy H, Valente EM, Gorman S, Williams R, McHale DP, Wood JN, Gribble FM, Woods CG (2006) An SCN9A channelopathy causes congenital inability to experience pain. Nature 444:894–898
Craig W (1887) Manual of materia medica and therapeutics, 5th edn. Livingstone, Edinburgh
Cummins TR, Waxman SG (1997) Downregulation of tetrodotoxin-resistant sodium currents and upregulation of a rapidly repriming tetrodotoxin-sensitive sodium current in small spinal sensory neurons after nerve injury. J Neurosci 17:3503–3514
Cummins TR, Sheets PL, Waxman SG (2007) The roles of sodium channels in nociception: Implications for mechanisms of pain. Pain 131:243–257
De Col R, Messlinger K, Carr RW (2008) Conduction velocity is regulated by sodium channel inactivation in unmyelinated axons innervating the rat cranial meninges. J Physiol 586:1089–1103
Dekker LV, Daniels Z, Hick C, Elsegood K, Bowden S, Szestak T, Burley JR, Southan A, Cronk D, James IF (2005) Analysis of human NaV1.8 expressed in SH-SY5Y neuroblastoma cells. Eur J Pharmacol 528:52–58
DeToledo JC (2000) Lidocaine and seizures. Ther Drug Monit 22:320–322
Devor M (2006) Sodium channels and mechanisms of neuropathic pain. J Pain 7(Suppl 1):S3–S12
Dib-Hajj S, Black JA, Cummins TR, Waxman SG (2002) NaN/NaV1.9: a sodium channel with unique properties. Trends Neurosci 25:253–259
Dib-Hajj SD, Rush AM, Cummins TR, Hisama FM, Novella S, Tyrrell L, Marshall L, Waxman SG (2005) Gain-of-function mutation in NaV1.7 in familial erythromelalgia induces bursting of sensory neurons. Brain 128:1847–1854
Dick IE, Brochu RM, Purohit Y, Kaczorowski GJ, Martin WJ, Priest BT (2007) Sodium channel blockade may contribute to the analgesic efficacy of antidepressants. J Pain 8:315–324
Docherty RJ, Farrag KJ (2006) The effect of dibutyryl cAMP on tetrodotoxin-sensitive and -resistant voltage-gated sodium currents in rat dorsal root ganglion neurons and the consequences for their sensitivity to lidocaine. Neuropharmacology 51:1047–1057
Docherty RJ, Charlesworth G, Farrag K, Bhattacharjee A, Costa S (2005) The use of the rat isolated vagus nerve for functional measurements of the effect of drugs in vitro. J Pharm Tox Methods 51:235–242
Dong XW, Jia Y, Lu SX, Zhou X, Cohen-Williams M, Hodgson R, Li H, Priestley T (2008) The antipsychotic drug, fluphenazine, effectively reverses mechanical allodynia in rat models of neuropathic pain. Psychopharmacology 195:559–568
Dunlop R, Davies RJ, Hockley J, Turner P (1988) Analgesic effects of oral flecainide. Lancet 331:420–421
Eisenberg E, River Y, Shifrin A, Krivoy N (2007) Antiepileptic drugs in the treatment of neuropathic pain. Drugs 67:1265–1289
Ekberg J, Adams DJ (2006) Neuronal voltage-gated sodium channel subtypes: key roles in inflammatory and neuropathic pain. Int J Biochem Cell Biol. 38:2005–2010
Ekberg J, Craik DJ, Adams DJ (2008) Conotoxin modulation of voltage-gated sodium channels. Int J Biochem Cell Biol 40(11):2363–2368. doi:10.1016/j.biocel.2007.08.017
England S, Bevan S, Docherty RJ (1996) PGE2 modulates the tetrodotoxin-resistant sodium current in neonatal rat dorsal root ganglion neurones via the cyclic AMP-protein kinase A cascade. J Physiol 495:429–440
Farrag KJ, Costa SK, Docherty RJ (2002) Differential sensitivity to tetrodotoxin and lack of effect of prostaglandin E2 on the pharmacology and physiology of propagated action potentials. Br J Pharmacol 135:1449–1456
Farrag KJ, Bhattacharjee A, Docherty RJ (2008) A comparison of the effects of veratridine on tetrodotoxin-sensitive and tetrodotoxin-resistant sodium channels in isolated rat dorsal root ganglion neurons. Pflugers Arch 455:929–938
Felts PA, Yokoyama S, Dib-Hajj S, Black JA, Waxman SG (1997) Sodium channel alpha-subunit mRNAs I, II, III, NaG, Na6 and hNE (PN1): different expression patterns in developing rat nervous system. Brain Res Mol Brain Res 45:71–82
Fitzgerald EM, Okuse K, Wood JN, Dolphin AC, Moss SJ (1999) cAMP-dependent phosphorylation of the tetrodotoxin-resistant voltage-dependent sodium channel SNS. J Physiol 516:433–446
Fraser SP, Salvador V, Manning EA, Mizal J, Altun S, Raza M, Berridge RJ, Djamgoz MB (2003) Contribution of functional voltage-gated Na+ channel expression to cell behaviors involved in the metastatic cascade in rat prostate cancer: I. Lateral motility. J Cell Physiol 195:479–487
Frohnwieser B, Weigl L, Schreibmayer W (1995) Modulation of cardiac sodium channel isoform by cyclic AMP dependent protein kinase does not depend on phosphorylation of serine 1504 in the cytosolic loop interconnecting transmembrane domains III and IV. Pflugers Arch 430:751–753
Gebhardt C, Breustedt JM, Nöldner M, Chatterjee SS, Heinemann U (2001) The antiepileptic drug losigamone decreases the persistent Na+ current in rat hippocampal neurons. Brain Res 920:27–31
Ghatapande AS, Sikdar SK (1997) Competition for binding between veratridine and KIFMK: an open channel blocking peptide of the RIIA sodium channel. J Membr Biol 160:177–182
Gold MS, Thut PD (2001) Lithium increases potency of lidocaine-induced block of voltage-gated Na+ currents in rat sensory neurons in vitro. J Pharmacol Exp Ther 299:705–711
Gold MS, Reichling DB, Shuster MJ, Levine JD (1996) Hyperalgesic agents increase a tetrodotoxin-resistant Na+ current in nociceptors. Proc Natl Acad Sci USA 93:1108–1112
Gold MS, Levine JD, Correa AM (1998) Modulation of TTX-R INa by PKC and PKA and their role in PGE2-induced sensitization of rat sensory neurons in vitro. J Neurosci 18:10345–10355
Goldberg YP, MacFarlane J, MacDonald ML, Thompson J, Dube MP, Mattice M, Fraser R, Young C, Hossain S, Pape T, Payne B, Radomski C, Donaldson G, Ives E, Cox J, Younghusband HB, Green R, Duff A, Boltshauser E, Grinspan GA, Dimon JH, Sibley BG, Andria G, Toscano E, Kerdraon J, Bowsher D, Pimstone SN, Samuels ME, Sherrington R, Hayden MR (2007) Loss-of-function mutations in the NaV1.7 gene underlie congenital indifference to pain in multiple human populations. Clin Genet 71:311–319
Goldin AL, Snutch T, Lubbert H, Dowsett A, Marshall J, Auld V, Downey W, Fritz LC, Lester HA, Dunn R (1986) Messenger RNA coding for only the alpha subunit of the rat brain Na channel is sufficient for expression of functional channels in Xenopus oocytes. Proc Natl Acad Sci USA 83:7503–7507
Goudet C, Chi C-W, Tytgat J (2002) An overview of toxins and genes from the venom of the Asian scorpion Buthus martensi Karsch. Toxicon 40:1239–1258
Gould HJ 3rd, England JD, Liu ZP, Levinson SR (1998) Rapid sodium channel augmentation in response to inflammation induced by complete Freund's adjuvant. Brain Res 802:69–74
Gould HJ 3rd, England JD, Soignier RD, Nolan P, Minor LD, Liu ZP, Levinson SR, Paul D (2004) Ibuprofen blocks changes in Nav 1.7 and NaV 1.8 sodium channels associated with complete Freund's adjuvant-induced inflammation in rat. J Pain 5:270–280
Grant AO, Chandra R, Keller C, Carboni M, Starmer CF (2000) Block of wild-type and inactivation deficient sodium channels IFM/QQQ stably expressed in mammalian cells. Biophysical J 79:3019–3035
Guven M, Bozdemir H, Gunay I, Sarica Y, Kahraman I, Koc F (2006) The actions of lamotrigine and levetiracetam on the conduction properties of isolated rat sciatic nerve. Eur J Pharmacol 553:129–134
Guy HR, Seetharamulu P (1986) Molecular model of the action potential sodium channel. Proc Natl Acad Sci USA 83:508–512
Hartshorne RP, Catterall WA (1981) Purification of the saxitoxin receptor of the sodium channel from rat brain. Proc Natl Acad Sci USA 78:4620–4624
Hartshorne RP, Catterall WA (1984) The sodium channel from rat brain. Purification and subunit composition. J Biol Chem 259:1667–1675
Hartshorne RP, Messner DJ, Coppersmith JC, Catterall WA (1984) The saxitoxin receptor of the sodium channel from rat brain. Evidence for two nonidentical beta subunits. J Biol Chem 257:13888–13891
Heinemann SH, Terlau H, Imoto K (1992) Molecular basis for pharmacological differences between brain and cardiac sodium channels. Pflugers Arch 422:90–92
Hille B (1975) The receptor for tetrodotoxin and saxitoxin. A structural hypothesis. Biophys J 15:615–619
Hille B (1977) Local anesthetics: hydrophilic and hydrophobic pathways for the drug receptor reaction. J Gen Physiol 69:497–515
Hille B (2001) Ion channels of excitable membranes, 3rd edn. Sinauer, Sunderland
Hui K, Lipkind G, Fozzard HA, French RJ (2002) Electrostatic and steric contributions to block of the skeletal muscle sodium channel by mu-conotoxin. J Gen Physiol 119:45–54
Hunt LW, Frigas E, Butterfield JH, Kita H, Blomgren J, Dunnette SL, Offord KP, Gleich GJ (2004) Treatment of asthma with nebulized lidocaine: a randomized, placebo-controlled study. J Allergy Clin Immunol 113:853–859
Ichimata M, Ikebe H, Yoshitake S, Hattori S, Iwasaka H, Noguchi T (2001a) Analgesic effects of flecainide on postherpetic neuralgia. Int J Clin Pharmacol Res 21:15–19
Ichimata M, Kitano T, Ikebe H, Iwasaka H, Noguchi T (2001b) Flecainide reverses neuropathic pain and suppresses ectopic nerve discharge in rats. Neuroreport 12:1869–1873
Ikeda SR, Scholfield GG, Weight FF (1986) Na+ and Ca2+ currents of acutely isolated adult rat nodose ganglion cells. J Neurophysiol 55:527–539
Ilyin VI, Pomonis JD, Whiteside GT, Harrison JE, Pearson MS, Mark L, Turchin PI, Gottshall S, Carter RB, Nguyen P, Hogenkamp DJ, Olanrewaju S, Benjamin E, Woodward RM (2006) Pharmacology of 2-[4-(4-chloro-2-fluorophenoxy)phenyl]-pyrimidine-4-carboxamide: a potent, broad-spectrum state-dependent sodium channel blocker for treating pain states. J Pharmacol Exp Ther 318:1083–1093
Isom LL, De Jongh KS, Patton DE, Reber BF, Offord J, Charbonneau H, Walsh K, Goldin AL, Catterall WA (1992) Primary structure and functional expression of the beta 1 subunit of the rat brain sodium channel. Science 256:839–842
Isom LL, Ragsdale DS, De Jongh KS, Westenbroek RE, Reber BF, Scheuer T, Catterall WA (1995) Structure and function of the beta 2 subunit of brain sodium channels, a transmembrane glycoprotein with a CAM motif. Cell 83:433–442
Jarvis B, Coukell AJ (1998) Mexiletine. A review of its therapeutic use in painful diabetic neuropathy. Drugs 56:691–707
Jeglitsch G, Rein K, Baden DG, Adams DJ (1998) Brevetoxin-3 (PbTx-3) and its derivatives modulate single tetrodotoxin-sensitive sodium currents in rat sensory neurons. J Pharmacol Exp Ther 284:516–525
Jin X, Gereau RW 4th (2006) Acute p38-mediated modulation of tetrodotoxin-resistant sodium channels in mouse sensory neurons by tumor necrosis factor-alpha. J Neurosci 26:246–255
Keizer DW, West PJ, Lee EF, Yoshikami D, Olivera BM, Bulaj G, Norton RS (2003) Structural basis for tetrodotoxin-resistant sodium channel binding by mu-conotoxin SmIIIA. J Biol Chem 278:46805–46813
Kerr NC, Gao Z, Holmes FE, Hobson SA, Hancox JC, Wynick D, James AF (2007) The sodium channel NaV1.5a is the predominant isoform expressed in adult mouse dorsal root ganglia and exhibits distinct inactivation properties from the full-length NaV1.5 channel. Mol Cell Neurosci 35:283–291
Kim CH, Oh Y, Chung JM, Chung K (2001) The changes in expression of three subtypes of TTX sensitive sodium channels in sensory neurons after spinal nerve ligation. Brain Res Mol Brain Res 95, 153–161
Ko SH, Jochnowitz N, Lenkowski PW, Batts TW, Davis GC, Martin WJ, Brown ML, Patel MK (2006) Reversal of neuropathic pain by alpha-hydroxyphenylamide: a novel sodium channel antagonist. Neuropharmacology 50:865–873
Kuo CC (1998) A common anticonvulsant binding site for phenytoin, carbamazepine, and lamotrigine in neuronal Na+ channels. Mol Pharmacol 54:712–721
Kuo CC, Bean BP (1994) Slow binding of phenytoin to inactivated sodium channels in rat hippocampal neurons. Mol Pharmacol 46:716–725
Kuo CC, Lu L (1997) Characterization of lamotrigine inhibition of Na+ channels in rat hippocampal neurones. Br J Pharmacol 121:1231–1238
Kyle DJ, Ilyin VI (2006) Sodium channel blockers. J Med Chem 50:2583–2588
Lai HC, Jan LY (2006) The distribution and targeting of neuronal voltage-gated ion channels. Nat Rev Neurosci 7:548–562
Lai J, Porreca F, Hunter JC, Gold MS (2004) Voltage-gated sodium channels and hyperalgesia. Ann Rev Pharmacol Toxicol 44:371–397
Lampert A, Hains BC, Waxman SG (2006) Upregulation of persistent and ramp sodium current in dorsal horn neurons after spinal cord injury. Exp Brain Res 174:660–666
Lang DG, Wang CM, Cooper BR (1993) Lamotrigine, phenytoin and carbamazepine interactions on the sodium current present in N4TG1 mouse neuroblastoma cells. J Pharmacol Exp Ther 266(2):829–835
Leffler A, Herzog RI, Dib-Hajj SD, Waxman SG, Cummins TR (2005) Pharmacological properties of neuronal TTX-resistant sodium channels and the role of a critical serine pore residue. Pflugers Arch 451:454–463
Leffler A, Reiprich A, Mohapatra DP, Nau C (2007) Use-dependent block by lidocaine but not by amitriptyline is more pronounced in tetrodotoxin (TTX)-resistant than in TTX-sensitive Na+ channels. J Pharm Exp Ther 320:354–364
Leipold E, Hansel A, Olivera BM, Terlau H, Heinemann SH (2005) Molecular interaction of delta-conotoxins with voltage-gated sodium channels. FEBS Lett 579:3881–3884
Leipold E, Hansel A, Borges A, Heinemann SH (2006) Subtype specificity of scorpion beta-toxin Tz1 interaction with voltage-gated sodium channels is determined by the pore loop of domain 3. Mol Pharmacol 70:340–347
Li M, West JW, Lai Y, Scheuer T, Catterall WA (1992) Functional modulation of brain sodium channels by cAMP-dependent phosphorylation. Neuron 8:1151–1159
Li HL, Hadid D, Ragsdale DS (2002) The batrachotoxin receptor on the voltage-gated sodium channel is guarded by the channel activation gate. Mol Pharmacol 61:905–912
Li RA, Ennis IL, Xue T, Nguyen HM, Tomaselli GF, Goldin AL, Marbán E (2003) Molecular basis of isoform-specific micro-conotoxin block of cardiac, skeletal muscle, and brain Na+ channels. J Biol Chem 278:8717–8724
Liberatore AM, Schulz J, Favre-Guilmard C, Pommier J, Lannoy J, Pawlowski E, Barthelemy MA, Huchet M, Auguet M, Chabrier PE, Bigg D (2007) Butyl 2-(4-[1.1′-biphenyl]-4-yl-1H-imidazol-2-yl)ethylcarbamate, a potent sodium channel blocker for the treatment of neuropathic pain. Bioorg Med Chem Lett 17:1746–1749
Lindia JA, Kohler MG, Martin WJ, Abbadie C (2005) Relationship between sodium channel NaV1.3 expression and neuropathic pain behavior in rats. Pain 117:145–153
Lim TKY, MacLeod BA, Ries CR, Schwartz SKW (2007) The quaternary lidocaine derivative, QX-314, produces long-lasting local anesthesia in animal models in vivo. Anesthesiology 107:305–311
Lipkind GM, Fozzard HA (1994) A structural model of the tetrodotoxin and saxitoxin binding site of the Na+ channel. Biophys J 66:1–13
Lipkind GM, Fozzard HA (2005) Molecular modeling of local anesthetic drug binding by voltage-gated sodium currents. Mol Pharmacol 68:1611–1622
Liu G, Yarov-Yarovoy V, Nobbs M, Clare JJ, Scheuer T, Catterall WA (2003) Differential interactions of lamotrigine and related drugs with transmembrane segment IVS6 of voltage-gated sodium channels. Neuropharmacology 44:413–422
Liu CJ, Priest BT, Bugianesi RM, Dulski PM, Felix JP, Dick IE, Brochu RM, Knaus H-G, Middleton RE, Kaczorowski GJ, Slaughter RS, Garcia ML, Kohler MG (2006) A high-capacity membrane potential FRET-based assay for NaV1.8 channels. Assay Drug Dev Technol 4:37–48
Lombet A, Bidard JN, Lazdunski M (1987) Ciguatoxin and brevetoxins share a common receptor site on the neuronal voltage-dependent Na+ channel. FEBS Lett 219:355–359
Lönnendonker U (1994) Use dependence of guanidinium toxins in frog myelinated nerve: evidence for features of native voltage-gated sodium channels. Prog Neurobiol 42:359–374
Maertens C, Cuypers E, Amininasab M, Jalali A, Vatanpour H, Tytgat J (2006) Potent modulation of the voltage-gated sodium channel NaV1.7 by OD1, a toxin from the scorpion Odonthobuthus doriae. Mol Pharmacol 70:405–414
Matsuki N, Quandt FN, Ten Eick RE, Yeh JZ (1984) Characterization of the block of sodium channels by phenytoin in mouse neuroblastoma cells. J Pharmacol Exp Ther 228:523–530
Matsumoto S, Yoshida S, Ikeda M, Tanimoto T, Saiki C, Takeda M, Shima Y, Ohta H (2007) Effect of 8-bromo-cAMP on the tetrodotoxin-resistant sodium (NaV1.8) current in small-diameter nodose ganglion neurones. Neuropharmacology 52:904–924
McLeane G (2007) Intravenous lidocaine: an outdated or underutilized treatment for pain. J Palliat Med 10:798–805
McNulty MM, Edgerton GB, Shah RD, Hanck DA, Fozzard HA, Lipkind GM (2007) Charge at the lidocaine binding site residue Phe-1759 affects permeation in human cardiac voltage-gated sodium channels. J Physiol 581:741–755
Messner DJ, Catterall WA (1985) The sodium channel from rat brain. Separation and characterization of subunits. J Biol Chem 260:10597–10604
Middleton RE, Warren VA, Kraus RL, Hwang JC, Liu CJ, Dai G, Brochu RM, Kohler MG, Gao YD, Garsky VM, Bogusky MJ, Mehl JT, Cohen CJ, Smith MM (2002) Two tarantula peptides inhibit activation of multiple sodium channels. Biochemistry 41:14734–14747
Morgan K, Stevens EB, Shah B, Cox PJ, Dixon AK, Lee K, Pinnock RD, Hughes J, Richardson PJ, Mizuguchi K, Jackson AP (2000) Beta 3: an additional auxiliary subunit of the voltage-sensitive sodium channel that modulates channel gating with distinct kinetics. Proc Natl Acad Sci USA 97:2308–2313
Murphy BJ, Rossie S, De Jongh KS, Catterall WA (1993) Identification of the sites of selective phosphorylation and dephosphorylation of the rat brain Na+ channel alpha subunit by cAMP-dependent protein kinase and phosphoprotein phosphatases. J Biol Chem 268:27355–27362
Nakamura S, Atsuta Y (2005) Effect of sodium channel blocker (mexiletine) on pathological ectopic firing pattern in a rat chronic constriction nerve injury model. J Orthop Sci 10:315–320
Narahashi T (1986) Toxins that modulate the sodium channel gating mechanism. Ann N Y Acad Sci 479:133–151
Narahashi T, Frazier DT, Moore JW (1972) Comparison of tertiary and quaternary amine local anesthetics in their ability to depress membrane ionic conductances. J Neurobiol 3:267–276
Nau C, Wang GK (2004) Interactions of local anesthetics with voltage-gated Na+ channels. J Membr Biol 201:1–8
Noda M (1993) Structure and function of sodium channels. Ann N Y Acad Sci 707:20–37
Oh Y, Sashihara S, Black JA, Waxman SG (1995) Na+ channel beta 1 subunit mRNA: differential expression in rat spinal sensory neurons. Brain Res Mol Brain Res 30:357–61
O'Reilly AO, Khambay BP, Williamson MS, Field LM, Wallace BA, Davies TG (2006) Modelling insecticide-binding sites in the voltage-gated sodium channel. Biochem J 396:255–263
Osawa Y, Oda A, Iida H, Tanahashi S, Dohi S (2004) The effects of class Ic antiarrhythmics on tetrodotoxin-resistant Na+ currents in rat sensory neurons. Anesth Analg 99:464–471
Ostman JAR, Nassar MA, Wood JN, Baker MD (2008) GTP up-regulated persistent Na+ current and enhanced nociceptor excitability require NaV1.9. J Physiol 586:1077–1087
Padilla F, Couble ML, Coste B, Maingret F, Clerc N, Crest M, Ritter AM, Magloire H, Delmas P (2007) Expression and localization of the NaV1.9 sodium channel in enteric neurons and in trigeminal sensory endings: implication for intestinal reflex function and orofacial pain. Mol Cell Neurosci 35:138–152
Patton DE, Goldin AL (1991) A voltage-dependent gating transition induces use-dependent block by tetrodotoxin of rat IIA sodium channels expressed in Xenopus oocytes. Neuron 7:637–647
Pearn J (2001) Neurology of ciguatera. J Neurol Neurosurg Psychiatr 70:4–8
Pratt CM, Moye LA (1990) The cardiac arrhythmia suppression trial: background, interim results and implications. Am J Cardiol 65:20B–29B
Priest BT, Blumenthal KM, Smith JJ, Warren VA, Smith MM (2007) ProTx-I and ProTx-II: gating modifiers of voltage-gated sodium channels. Toxicon 49:194–201
Ragsdale DS, Scheuer T, Catterall WA (1991) Frequency and voltage-dependent inhibition of type IIA Na+ channels, expressed in a mammalian cell line, by local anesthetic, antiarrhythmic, and anticonvulsant drugs. Mol Pharmacol 40:756–65
Ragsdale DS, McPhee JC, Scheuer T, Catterall WA (1994) Molecular determinants of state-dependent block of Na+ channels by local anaesthetics. Science 265:1724–1728
Ragsdale DS, McPhee JC, Scheuer T, Catterall WA (1996) Common molecular determinants of local anesthetic, antiarrhythmic, and anticonvulsant block of voltage-gated Na+ channels. Proc Natl Acad Sci USA 93:9270–9275
Ratcliffe CF, Westenbroek RE, Curtis R, Catterall WA (2001) Sodium channel beta1 and beta3 subunits associate with neurofascin through their extracellular immunoglobulin-like domain. J Cell Biol 154:427–434
Renganathan M, Cummins TR, Waxman SG (2001) Contribution of NaV1.8 sodium channels to action potential electrogenesis in DRG neurons. J Neurophysiol 86:629–640
Renganathan M, Dib-Hajj S, Waxman SG (2002) NaV1.5 underlies the ‘third TTX-R sodium current’ in rat small DRG neurons. Brain Res Mol Brain Res 106:70–82
Ritter AM, Ritchie C, Martin WJ (2007) Relationship between the firing frequency of injured peripheral neurons and inhibition of firing by sodium channel blockers. J Pain 8:287–295
Rogawski MA, Löscher W (2004) The neurobiology of antiepileptic drugs for the treatment of nonepileptic conditions. Nat Med 10:685–692
Roy ML, Narahashi T (1992) Differential properties of tetrodotoxin-sensitive and tetrodotoxin-resistant sodium channels in rat dorsal root ganglion neurons. J Neurosci 12:2104–2111
Rush AM, Elliott JR (1997) Phenytoin and carbamazepine: differential inhibition of sodium currents in small cells from adult rat dorsal root ganglia. Neurosci Lett 226:95–98
Rush AM, Dib-Hajj SD, Waxman SG (2005) Electrophysiological properties of two axonal sodium channels, NaV1.2 and NaV1.6, expressed in mouse spinal sensory neurones. J Physiol 564:803–815
Rush AM, Cummins TR, Waxman SG (2007) Multiple sodium channels and their roles in electrogenesis within dorsal root ganglion neurons. J Physiol 579:1–14
Saab CY, Cummins TR, Dib-Hajj SD, Waxman SG (2002) Molecular determinant of NaV1.8 sodium channel resistance to the venom from the scorpion Leiurus quinquestraitus hebraeus. Neurosci Lett 331:79–82
Salgado VL, Yeh JZ, Narahashi T (1986) Use- and voltage-dependent block of the sodium channel by saxitoxin. Ann N Y Acad Sci 479:84–95
Sasaki K, Makita N, Sunami A, Sakurada H, Shirai N, Yokoi H, Kimura A, Tohse N, Hiraoka M, Kitabatake A (2004) Unexpected mexiletine responses of a mutant cardiac Na+ channel implicate the selectivity filter as a structural determinant of antiarrhythmic drug access. Mol Pharmacol 66:330–336
Satin J, Kyle JW, Chen M, Bell P, Cribbs LL, Fozzard HA, Rogart RB (1992) A mutant of TTX-resistant cardiac sodium channels with TTX-sensitive properties. Science 256:1202–1205
Sato K, Ishida Y, Wakamatsu K, Kato R, Honda H, Ohizumi Y, Nakamura H, Ohya M, Lancelin JM, Kohda D, Inagaki F (1991) Active site of mu-conotoxin GIIIA, a peptide blocker of muscle sodium channels. J Biol Chem 266:16989–16991
Scheib H, McLay I, Guex N, Clare JJ, Blaney FE, Dale TJ, Tate SN, Robertson GM (2006) Modelling the pore structure of voltage-gated sodium channels in closed, open, and fast-inactivated conformation reveals details of site 1 toxin and local anesthetic binding. J Mol Model 12:813–822
Scholz A, Kuboyama N, Hempelmann G, Vogel W (1998) Complex blockade of TTX-resistant Na+ currents by lidocaine and bupivacaine reduce firing frequency in DRG neurons. J Neurophysiol 79:1746–1754
Schwarz JR, Grigat G (1989) Phenytoin and carbamazepine: potential- and frequency-dependent block of Na currents in mammalian myelinated nerve fibers. Epilepsia 30:286–294
Schneider M, Datta S, Strichartz G (1991) A preferential inhibition of impulses in C-fibers of the rabbit vagus nerve by veratridine, an activator of sodium channels. Anaesthesiology 74:270–280
Segal MM, Douglas AF (1997) Late sodium channel openings underlying epileptiform activity are preferentially diminished by the anticonvulsant phenytoin. J Neurophysiol 77:3021–3034
Shah BS, Stevens EB, Gonzalez MI, Bramwell S, Pinnock RD, Lee K, Dixon AK (2000) Beta3, a novel auxiliary subunit for the voltage-gated sodium channel, is expressed preferentially in sensory neurons and is upregulated in the chronic constriction injury model of neuropathic pain. Eur J Neurosci 12:3985–3990
Shao PP, Ok D, Fisher MH, Garcia ML, Kaczorowski GJ, Li C, Lyons KA, Martin WJ, Meinke PT, Priest BT, Smith MM, Wyvratt MJ, Ye F, Parsons WH (2005) Novel cyclopentane dicarboxamide sodium channel blockers as a potential treatment for chronic pain. Bioorg Med Chem Lett 15:1901–1907
Sheets MF, Hanck DA (2007) Outward stabilization of the S4 segments in domains III and IV enhances lidocaine block of sodium channels. J Physiol 582:317–334
Shon KJ, Olivera BM, Watkins M, Jacobsen RB, Gray WR, Floresca CZ, Cruz LJ, Hillyard DR, Brink A, Terlau H, Yoshikami D (1998) mu-Conotoxin PIIIA, a new peptide for discriminating among tetrodotoxin-sensitive Na channel subtypes. J Neurosci 18:4473–4481
Sivilotti L, Okuse K, Akopian AN, Moss S, Wood JN (1997) A single serine residue confers tetrodotoxin insensitivity on the rat sensory-neuron-specific sodium channel SNS. FEBS Lett 409:49–52
Smith KJ (2007) Sodium channels and multiple sclerosis: roles in symptom production, damage and therapy. Brain Pathol 17:230–242
Smith RD, Goldin AL (1996) Phosphorylation of brain sodium channels in the I–II linker modulates channel function in Xenopus oocytes. J Neurosci 16:1965–1974
Smith RD, Goldin AL (1998) Functional analysis of the rat I sodium channel in Xenopus oocytes. J Neurosci 18:811–820
Smith RD, Goldin AL (2000) Potentiation of rat brain sodium channel currents by PKA in Xenopus oocytes involves the I–II linker. Am J Physiol Cell Physiol 278:C638–C645
Smith JJ, Cummins TR, Alphy S, Blumenthal KM (2007) Molecular interactions of the gating modifier toxin ProTx-II with NaV1.5: implied existence of a novel toxin binding site coupled to activation. J Biol Chem 282:12687–12697
Song JH, Nagata K, Huang CS, Yeh JZ, Narahashi T (1996) Differential block of two types of sodium channels by anticonvulsants. Neuroreport 7:3031–3036
Spina E, Perugi G (2004) Antiepileptic drugs: indications other than epilepsy. Epileptic Disord 6:57–75
Srinivasan J, Schachner M, Catterall WA (1998) Interaction of voltage-gated sodium channels with the extracellular matrix molecules tenascin-C and tenascin-R. Proc Natl Acad Sci USA 95:15753–15757
Ständker L, Béress L, Garateix A, Christ T, Ravens U, Salceda E, Soto E, John H, Forssmann WG, Aneiros A (2006) A new toxin from the sea anemone Condylactis gigantea with effect on sodium channel inactivation. Toxicon 48:211–220
Starmer CF, Grant AO, Strauss HC (1984) Mechanisms of use-dependent block of sodium channels in excitable membranes by local anesthetics. Biophys J 46:15–27
Stephan MM, Potts JF, Agnew WS (1994) The microI skeletal muscle sodium channel: mutation E403Q eliminates sensitivity to tetrodotoxin but not to mu-conotoxins GIIIA and GIIIB. J Membr Biol 137:1–8
Strachan LC, Lewis RJ, Nicholson GM (1999) Differential actions of pacific ciguatoxin-1 on sodium channel subtypes in mammalian sensory neurons. J Pharmacol Exp Ther 288:379–388
Strichartz GR (1973) The inhibition of sodium currents in myelinated nerve by quaternary derivatives of lidocaine. J Gen Physiol 62:37–57
Stummann TC, Salvati P, Fariello RG, Faravelli L (2005) The anti-nociceptive agent ralfinamide inhibits tetrodotoxin-resistant and tetrodotoxin-sensitive Na+ currents in dorsal root ganglion neurons. Eur J Pharmacol 510:197–208
Su X, Riedel ES, Leon LA, Laping NJ (2007) Pharmacologic evaluation of pressor and visceromotor reflex responses to bladder distension. Neurourol Urodyn 27:249–253
Sugai K (2007) Treatment of convulsive status epilepticus in infants and young children in Japan. Acta Neurol Scand Suppl 186:62–70
Sun GC, Werkman TR, Battefeld A, Clare JJ, Wadman WJ (2007) Carbamazepine and topiramate modulation of transient and persistent sodium currents studied in HEK293 cells expressing the NaV1.3 alpha-subunit. Epilepsia 48:774–782
Sunami A, Glasser IW, Fozzard HA (2000) A critical residue for isoforms difference in tetrodotoxin affinity is a molecular determinant of the external path for local anesthetics in the cardiac sodium channel. Proc Nat Acad Sci USA 97:2326–2331
Szallasi A, Cruz F, Geppetti P (2006) TRPV1: a therapeutic target for novel analgesic drugs? Tr Mol Med 12:545–554
Tabarean IV, Narahashi T (2001) Kinetics of modulation of tetrodotoxin-sensitive and tetrodotoxin-resistant sodium channels by tetramethrin and deltamethrin. J Pharm Exp Ther 299:988–997
Tan ZY, Mao X, Xiao H, Zhao ZQ, Ji YH (2001) Buthus martensi Karsch agonist of skeletal muscle RyR-1, a scorpion active polypeptide: antinociceptive effect on rat peripheral nervous system and spinal cord, and inhibition of voltage-gated Na+ currents in dorsal root ganglion neurons. Neurosci Lett 297:65–68
Tanahashi S, Iida H, Oda A, Osawa Y, Uchida M, Dohi S (2007) Effects of ifenprodil on voltage-gated tetrodotoxin-resistant Na+ channels in rat sensory neurons. Eur J Anaesthesiol 24:782–788
Tatebayashi H, Narahashi T (1994) Differential mechanism of action of the pyrethroid tetramethrin on tetrodotoxin-sensitive and tetrodotoxin-resistant sodium channels. J Pharmacol Exp Ther 270:595–603
Taverna S, Mantegazza M, Franceschetti S, Avanzini G (1998) Valproate selectively reduces the persistent fraction of Na+ current in neocortical neurons. Epilepsy Res 32:304–308
Terlau H, Heinemann SH, Stuhmer W, Pusch M, Conti F, Imoto K, Numa S (1991) Mapping the site of block by tetrodotoxin and saxitoxin of sodium channel II. FEBS Lett 293:93–96
Todorovic SM, Rastogi AJ, Jevtovic-Todorovic V (2003) Potent analgesic effects of anticonvulsants on peripheral thermal nociception in rats. Br J Pharmacol 140:255–260
Toledo-Aral JJ, Moss BL, He ZJ, Koszowski AG, Whisenand T, Levinson SR, Wolf JJ, Silos-Santiago I, Halegoua S, Mandel G (1997) Identification of PN1, a predominant voltage-dependent sodium channel expressed principally in peripheral neurons. Proc Natl Acad Sci USA 94:1527–1532
Trainer VL, Baden DG, Catterall WA (1994) Identification of peptide components of the brevetoxin receptor site of rat brain sodium channels. J Biol Chem 269:19904–19909
Tzeng JI, Cheng KI, Huang KL, Chen YW, Chu KS, Chu CC, Wang JJ (2007) The cutaneous analgesic effect of class I antiarrhythmic drugs. Anesth Analg 104:955–958
Ulbricht W (1998) Effects of veratridine on sodium currents and fluxes. Rev Physiol Biochem Pharmacol 133:1–54
Veneroni O, Maj R, Calabresi M, Faravelli L, Fariello RG, Salvati P (2003) Anti-allodynic effect of NW-1029, a novel Na+ channel blocker, in experimental animal models of inflammatory and neuropathic pain. Pain 102:17–25
Vickery RG, Amagasu SM, Chang R, Mai N, Kauman E, Martin J, Hembrador J, O'Keefe MD, Gee C, Marquess D, Smith JA (2004) Comparison of the pharmacological properties of rat NaV1.8 with Rat NaV 1.2a and human NaV1.5 voltage-gated sodium channel subtypes using a membrane potential sensitive dye and FLIPR. Receptors Channels 10:11–23
Vijayaragavan K, Boutjdir M, Chahine M (2004) Modulation of NaV1.7 and NaV1.8 peripheral nerve sodium channels by protein kinase A and protein kinase C. J Neurophysiol 91: 1556–1569
Von Gunten CF, Eappen S, Cleary JF, Taylor SG 4th, Moots P, Regevik N, Cleeland C, Cella D (2007) Flecainide for the treatment of chronic neuropathic pain: a Phase II trial. Palliat Med 21:667–672
Wang S-Y, Wang GK (2003) Voltage-gated sodium channels as primary targets of diverse lipid-soluble neurotoxins. Cell Signal 15:151–159
Wang GK, Brodwick MS, Eaton DC, Strichartz GR (1987) Inhibition of sodium currents by local anaesthetics in chloramine-T treated squid axons. The role of channel activation. J Gen Physiol 89:645–667
Wang S-Y, Mitchell J, Moczydlowski E, Wang GK (2004) Block of inactivation-deficient Na+ channels by local anaesthetics in stably transfected mammalian cells: evidence for drug binding along the activation pathway. J Gen Physiol 124:691–701
Wang CZ, Zhang H, Jiang H, Lu W, Zhao ZQ, Chi CW (2006) A novel conotoxin from Conus striatus, mu-SIIIA, selectively blocking rat tetrodotoxin-resistant sodium channels. Toxicon 47:122–132
Wang S-Y, Tikhonov DB, Zhorov BS, Mitchell J, Wang GK (2007) Serine-401 as a batrachotoxin- and local anesthetic-sensing residue in the human cardiac Na+ channel. Pflugers Arch 454: 277–287
Waxman SG (2006) Axonal conduction and injury in multiple sclerosis: the role of sodium channels. Nat Rev Neurosci 7:932–941
Waxman SG, Kocsis JD, Black JA (1994) Type III sodium channel mRNA is expressed in embryonic but not adult spinal sensory neurons, and is re-expressed following axotomy. J Neurophysiol 72:466–470
Weiser T (2006) Comparison of the effects of four Na+ channel analgesics on TTX-resistant Na+ currents in rat sensory neurons and recombinant NaV1.2 channels. Neurosci Lett 395:179–184
West JW, Patton DE, Scheuer T, Wang Y, Goldin AL, Catterall WA (1992) A cluster of hydrophobic amino acid residues required for fast Na+-channel inactivation. Proc Natl Acad Sci USA 89:10910–10914
Wiffen PJ, Rees J (2007) Lamotrigine for acute and chronic pain. Cochrane Database Syst Rev 2:CD006044
Williams BS, Felix JP, Priest BT, Brochu RM, Dai K, Hoyt SB, London C, Tang YS, Duffy JL, Parsons WH, Kaczorowski GJ, Garcia ML (2007) Characterization of a new class of potent inhibitors of the voltage-gated sodium channel NaV1.7. Biochemistry 46:14693–14703
Willow M, Catterall WA (1982) Inhibition of binding of [3H]batrachotoxinin A 20-alpha-benzoate to sodium channels by the anticonvulsant drugs diphenylhydantoin and carbamazepine. Mol Pharmacol 22:627–635
Willow M, Gonoi T, Catterall WA (1985) Voltage clamp analysis of the inhibitory actions of diphenylhydantoin and carbamazepine on voltage-sensitive sodium channels in neuroblastoma cells. Mol Pharmacol 27:549–558
Wittmack EK, Rush AM, Hudmon A, Waxman SG, Dib-Hajj SD (2005) Voltage-gated sodium channel NaV1.6 is modulated by p38 mitogen-activated protein kinase. J Neurosci 25:6621–6630
Wood JN, Boorman JP, Okuse K, Baker MD (2004) Voltage-gated sodium channels and pain pathways. J Neurobiol 61:55–71
Wright SN (2002) Comparison of aconitine-modified human heart (hH1) and rat skeletal muscle (mu1) Na+ channels: an important role for external Na+ ions. J Physiol 538:759–771
Xiao Y, Tang J, Hu W, Xie J, Maertens C, Tytgat J, Liang S (2005) Jingzhaotoxin-I, a novel spider neurotoxin preferentially inhibiting cardiac sodium channel inactivation. J Biol Chem 280:12069–12076
Yakehiro M, Yuki T, Yamaoka K, Furue T, Mori Y, Imoto K, Seyama I (2000) An analysis of the variations in potency of gryanotoxin analogs in modifying frog sodium channels of different subtypes. Mol Pharmacol 58:692–700
Yamane H, de Groat WC, Sculptoreanu A (2007) Effects of ralfinamide, a Na+ channel blocker, on firing properties of nociceptive dorsal root ganglion neurons of adult rats. Exp Neurol 208:63–72
Yarov-Yarovoy V, Brown J, Sharp EM, Clare JJ, Scheuer T, Catterall WA (2001) Molecular determinants of voltage-dependent gating and binding of pore-blocking drugs in transmembrane segment IIIS6 of the Na+ channel alpha subunit. J Biol Chem 276:20–27
Yarov-Yarovoy V, McPhee JC, Idsvoog D, Pate C, Scheuer T, Catterall WA (2002) Role of amino acid residues in transmembrane segments IS6 and IIS6 of the Na+ channel alpha subunit in voltage-dependent gating and drug block. J Med Chem 277:35393–35401
Ye JG, Wang CY, Li YJ, Tan ZY, Yan YP, Li C, Chen J, Ji YH (2000) Purification, cDNA cloning and function assessment of BmK abT, a unique component from the Old World scorpion species. FEBS Lett 479:136–140
Yu FH, Catterall WA (2003) Overview of the voltage-gated sodium channel family. Genome Biol 4:207
Yu FH, Westenbroek RE, Silos-Santiago I, McCormick KA, Lawson D, Ge P, Ferriera H, Lilly J, DiStefano PS, Catterall WA, Scheuer T, Curtis R (2003) Sodium channel beta4, a new disulfide-linked auxiliary subunit with similarity to beta2. J Neurosci 23:7577–7585
Zhang MM, Green BR, Catlin P, Fiedler B, Azam L, Chadwick A, Terlau H, McArthur JR, French RJ, Gulyas J, Rivier JE, Smith BJ, Norton RS, Olivera BM, Yoshikami D, Bulaj G (2007) Structure/function characterization of micro-conotoxin KIIIA, an analgesic, nearly irreversible blocker of mammalian neuronal sodium channels. J Biol Chem 282:30699–30706
Zhou X, Dong XW, Crona J, Maguire M, Priestley T (2003) Vinpocetine is a potent blocker of rat NaV1.8 tetrodotoxin-resistant sodium channels. J Pharmacol Exp Ther 306:498–504
Zhou X, Dong XW, Priestley T (2006) The neuroleptic drug, fluphenazine, blocks neuronal voltage-gated sodium channels. Brain Res 1106:72–81
Zimmermann K, Leffler A, Babes A, Cendan CM, Carr RW, Kobayashi J, Nau C, Wood JN, Reeh PW (2007) Sensory neuron sodium channel NaV1.8 is essential for pain at low temperatures. Nature 447:855–858
Zlotkin E (1999) The insect voltage-gated sodium channel as target of insecticides. Annu Rev Entemol 44:429–455
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Docherty, R.J., Farmer, C.E. (2009). The Pharmacology of Voltage-Gated Sodium Channels in Sensory Neurones. In: Canning, B., Spina, D. (eds) Sensory Nerves. Handbook of Experimental Pharmacology, vol 194. Springer, Berlin, Heidelberg. https://doi.org/10.1007/978-3-540-79090-7_15
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