NaV1.1 channels
| Channel name | NaV1.1 |
| Description | Voltage-gated sodium channel α subunit |
| Other names | Brain type I, rat 1, R-I |
| Molecular information | Human: 2009aa, P35498, X65362, chr. 2q24.3, SCN1A |
| Rat: 2009aa, P04775 NM_03975, chr. 3q21 | |
| Mouse: 2048aa, Q68V28, XM_61957, chr. 2 | |
| Associated subunits | β1, β2, β3, β4 |
| Functional assays | Voltage-clamp, neurotoxin-activated ion flux, voltage-sensitive dyes |
| Current | INa |
| Conductance | Not established |
| Ion selectivity | Na+ > K+ > Ca2+ |
| Activation | Va = –33 mV1 |
| Inactivation | Vh = –72 mV, th = 0.7 ms at –10 mV1 |
| 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 = 6 nM)1, saxitoxin; local anesthetic, antiepileptic, and antiarrhythmic drugs |
| Radioligands | [3H]saxitoxin, [3H]batrachotoxin, [125I]scorpion toxins |
| Channel distribution | Central neurons: primarily localized to cell bodies2; cardiac myocytes3 |
| Physiological functions | Action potential initiation and repetitive firing in neurons; excitation-contraction coupling in cardiac myocytes |
| Mutations and pathophysiology | Point mutations and deletions cause inherited febrile seizures, GEFS+, and severe myoclonic epilepsy of infancy4,5,6 |
| Pharmacological significance | Site of action of antiepileptic drugs; potential site of side effects of local anesthetics that enter the general circulation or cerebrospinal fluid |
aa, amino acids; chr., chromosome; GEFS+, generalized epilepsy with febrile seizures plus.
↵1. Clare JJ, Tate SN, Nobbs M, and Romanos MA (2000) Voltage-gated sodium channels as therapeutic targets. Drug Discov Today 5:506-520
↵2. Westenbroek RE, Merrick DK, and Catterall WA (1989) Differential subcellular localization of the RI and RII Na+ channel subtypes in central neurons. Neuron 3:695-704
↵3. 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
↵4. Escayg A, MacDonald BT, Meisler MH, Baulac S, Huberfeld G, An-Gourfinkel I, Brice A, LeGuern E, Moulard B, Chaigne D, et al. (2000) Mutations ofSCN1A, encoding a neuronal sodium channel, in two families with GEFS + 2. Nat Genet 24:343-345
↵5. Spampanato J, Escayg A, Meisler MH, and Goldin AL (2001) Functional effects of two voltage-gated sodium channel mutations that cause generalized epilepsy with febrile seizures plus type 2. J Neurosci 21:7481-7490
↵6. Nabbout R, Gennaro E, Dalla Bernardina B, Dulac O, Madia F, Bertini E, Capovilla G, Chiron C, Cristofori G, Elia M, et al. (2003) Spectrum of SCN1A mutations in severe myoclonic epilepsy of infancy. Neurology 60:1961-1967