NaV1.3 channels
| Channel name | NaV1.3 |
| Description | Voltage-gated sodium channel α subunit |
| Other names | Brain type 3, rat 3, R-III |
| Molecular information | Human: 1951aa, Q9NY46, XP0336775, NP008853, chr. 2q23-24, SCN3A |
| Rat: 1951aa, P08104, Y00766, NM_012647, chr. 3q24 | |
| Mouse: 2071aa, Q68V26, XM_355332, chr. 2 | |
| Associated subunits | β1 and β3 modulate inactivation; time course of expression parallels β31,2 |
| Functional assays | Voltage-clamp, neurotoxin-activated ion flux, voltage-sensitive dyes |
| Current | INa |
| Conductance | Not established |
| Ion selectivity | Na+ > K+ > Ca2+ |
| Activation | Va = –23 to –26 mV3,4 |
| Inactivation | Vh = –65 to –69 mV, τh = 0.8 to 1.5 ms at –10 mV3,4 |
| Activators | Veratridine, batrachotoxin, aconitine, grayanotoxin, and related natural organic toxins; β-scorpion toxins |
| Gating modifiers | α-Scorpion toxins, sea anemone toxins, and δ-conotoxins, which all slow inactivation |
| Blockers | Tetrodotoxin (EC50 = 4 nM),1 saxitoxin; local anesthetic, antiepileptic, and antiarrhythmic drugs |
| Radioligands | [3H]saxitoxin, [3H]batrachotoxin, [125I]scorpion toxins |
| Channel distribution | Central neurones: primarily expressed in embryonic and early prenatal life; preferentially localized in cell bodies in adult rat brain2,5,6; cardiac myocytes7 |
| Physiological functions | Action potential initiation and conduction; repetitive firing |
| Mutations and pathophysiology | Not fully established; up-regulated in dorsal root ganglion neurons and dorsal horn neurons in axotomy and other nerve injuries7,8; rapid recovery from inactivation contributes to hyperexcitability following nerve injury10 |
| Pharmacological significance | Site of action of antiepileptic drugs; potential site of side effects of local anesthetics that enter the general circulation or the cerebrospinal fluid |
aa, amino acids; chr., chromosome.
↵1. Meadows LS, Chen YH, Powell AJ, Clare JJ, and Ragsdale DS (2002) Functional modulation of human NaV1.3 sodium channels expressed in mammalian cells, by auxiliary β1, β2, and β3 subunits. Neuroscience 114:745-753
↵2. Shah BS, Stevens EB, Pinnock RD, Dixon AK, and Lee K (2001) Developmental expression of the novel voltage-gated sodium channel subunit β3 in rat CNS. J Physiol (Lond) 534:763-776
↵3. Chen YH, Dale TJ, Romanos MA, Whitaker WR, Xie XM, and Clare JJ (2000) Cloning, distribution and functional analysis of the type III sodium channel from human brain. Eur J Neurosci 12:4281-4289
↵4. Cummins TR, Aglieco F, Renganathan M, Herzog RI, Dib-Hajj SD, and Waxman SG (2001) NaV1.3 sodium channels: rapid repriming and slow closed-state inactivation display quantitative differences after expression in a mammalian cell line and in spinal sensory neurons. J Neurosci 21:5952-5961
↵5. Beckh S, Noda M, Lübbert H, and Numa S (1989) Differential regulation of three sodium channel messenger RNAs in the rat central nervous system during development. EMBO J 8:3611-3616
↵6. Westenbroek RE, Noebels JL, and Catterall WA (1992) Elevated expression of type II Na+ channels in hypomyelinated axons of shiverer mouse brain. J Neurosci 12:2259-2267
↵7. Maier SK, Westenbroek RE, Schenkman KA, Feigl EO, Scheuer T, and Catterall WA (2002) An unexpected role for brain-type sodium channels in coupling of cell surface depolarization to contraction in the heart, Proc Natl Acad Sci USA 99:4073-4078
↵8. Waxman SG, Kocsis JD, and 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 72:466-472
↵9. Hains BC, Saab CY, Klein JP, Craner MC, and Waxman SG (2004) Altered sodium channel expression in second-order spinal sensory neurons contributes to pain after peripheral nerve injury. J Neurosci 24:4832-4840
↵10. Cummins TC and Waxman SG (1997) Down-regulation of tetrodotoxin-resistant sodium currents and up-regulation of a rapidly-repriming tetrodotoxin-sensitive sodium current in spinal sensory neurons following nerve injury. J Neurosci 17:3503-3514