NaV1.2 channels
| Channel name | NaV1.2 |
| Description | Voltage-gated sodium channel α subunit |
| Other names | Brain type II, rat II, R-II |
| Molecular information | Human: 2005aa, Q99250, X65361, M94055, NM_021007, chr. 2q22-23, SCN2A |
| Rat: 2006aa, P04775, X03630, X61149, NM_012647, 3q24 | |
| Mouse: Q68V27, fragment only, 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 = –24 mV, τa < 0.4 ms at Va1,2 (see “Comments”) |
| Inactivation | Vh = –53 mV, τh = 8 ms at Va, th = 0.8 ms at 0 mV1,2 |
| Activators | Veratridine, batrachotoxin, aconitine, grayanotoxin, and related organic toxins; β-scorpion toxins |
| Gating modifiers | α-Scorpion toxins, sea anemone toxins, and δ-conotoxins, which all slow inactivation |
| Blockers | Tetrodotoxin (EC50 = 12 nM),3 saxitoxin; local anesthetic, antiepileptic, and antiarrhythmic drugs (EC50 = 11 mM for lidocaine in inactivated state) |
| Radioligands | [3H]saxitoxin (Kd = 1 nM),5 [3H]batrachotoxin, [125I]α-scorpion toxin (Kd = 2 nM),6 [125I]β-scorpion toxin (Kd = 0.2 nM)7 |
| Channel distribution | Central neurones: primarily localized to unmyelinated and premyelinated axons8,9,10 |
| Physiological functions | Action potential initiation and conduction, repetitive firing |
| Mutations and pathophysiology | A point mutation has been reported to cause inherited febrile seizures and epilepsy11 |
| Pharmacological significance | Site of action of antiepileptic drugs; probable site of side effects of local anesthetics that reach the general circulation or the cerebrospinal fluid |
| Comments | Values given for activation and inactivation parameters are for α subunits expressed alone in mammalian cells and measured with an intracellular solution containing aspartate or chloride2 as the primary anion; coexpression of different β subunits gives positive or negative shifts in voltage dependence |
aa, amino acids; chr., chromosome.
↵1. Mantegazza M, Yu FH, Catterall WA, and Scheuer T (2001) Role of the C-terminal domain in inactivation of brain and cardiac sodium channels. Proc Natl Acad Sci USA 98:15348-15353
↵2. Qu Y, Curtis R, Lawson D, Gilbride K, Ge P, DeStefano PS, Silos-Santiago I, Catterall WA, and Scheuer T (2001) Differential modulation of sodium channel gating and persistent sodium currents by the β1, β2, and β3 subunits. Mol Cell Neurosci 18:570-580
↵3. Noda M, Ikeda T, Kayano T, Suzuki H, Takeshima H, Kurasaki M, Takahashi H, and Numa S (1986) Existence of distinct sodium channel messenger RNAs in rat brain. Nature 320:188-192
↵4. Ragsdale DR, McPhee JC, Scheuer T, and 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
↵5. West JW, Scheuer T, Maechler L, and Catterall WA (1992) Efficient expression of rat brain type IIA Na+ channel α subunits in a somatic cell line. Neuron 8:59-70
↵6. Rogers JC, Qu Y, Tanada TN, Scheuer T, and Catterall WA (1996) Molecular determinants of high affinity binding of α-scorpion toxin and sea anemone toxin in the S3-S4 extracellular loop in domain IV of the Na+ channel α subunit. J Biol Chem 271:15950-15962
↵7. Cestèle S, Qu Y, Rogers JC, Rochat H, Scheuer T, and Catterall, WA (1998) Voltage sensor-trapping: enhanced activation of sodium channels by β-scorpion toxin bound to the S3-S4 loop in domain II. Neuron 21:919-931
↵8. 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
↵9. Boiko T, Rasband MN, Levinson SR, Caldwell JH, Mandel G, Trimmer JS. and Matthews G. (2001)Compact myelin dictates the differential targeting of two sodium channel isoforms in the same axon. Neuron 30:91-104
↵10. Kaplan MR, Cho MH, Ullian EM, Isom LL, Levinson SR, and Barres BA (2001) Differential control of clustering of the sodium channels NaV1.2 and NaV1.6 at developing CNS nodes of Ranvier. Neuron 30:105-119
↵11. Sugawara T, Tsurubuchi Y, Agarwala KL, Ito M, Fukuma G, Mazaki-Miyazaki E, Nagafuji H, Noda M, Imoto K, Wada K, et al. (2001) A missense mutation of the Na+ channel alpha II subunit gene NaV1.2 in a patient with febrile and afebrile seizures causes channel dysfunction. Proc Natl Acad Sci USA 98:6384-6389