NaV1.7 channels
| Channel name | Nav1.7 |
| Description | Voltage-gated sodium channel α subunit |
| Other names | PN1,1,2 hNE-Na,3 Nas4 |
| Molecular information | Human: 1977aa, X82835,3 chr. 2q24, SCN9A |
| Rat: 1984aa, AF000368, U795681,2 | |
| Mouse: chr. 2[36],5,6 Scn9A | |
| Associated subunits | β1, β2 |
| Functional assays | Voltage-clamp, neurotoxin-activated ion flux, voltage-sensitive dyes |
| Current | INa |
| Conductance | 19.5pS (for TTX-sensitive current in DRG neurons)7 |
| Ion selectivity | Na+ |
| Activation | Va = –31 mV (rat α subunit in Xenopus oocytes with macropatch)2 |
| Va = –45 mV (TTX-sensitive current in DRG neurons)7 | |
| Inactivation | Vh = –78 mV, τh = 0.46 and 20 ms at –30 mV, τh = 0.1 and 1.8 ms at 10 mV (rat α subunit in Xenopus oocytes with 10-s depolarizations using two-electrode voltage-clamp)2 |
| Vh = –60.5 mV (human α subunit in HEK cells with 2-s depolarizations using whole-cell patch clamp)3 | |
| Vh = –39.6 mV (human α subunit with β1 subunit in HEK cells with 2-s depolarizations using whole-cell patch clamp)3 | |
| Vh = –65 mV (TTX-sensitive current in DRG neurons with 50-ms to 1-s depolarizations using whole-cell patch clamp)7 | |
| Activators | Veratridine, batrachotoxin (based on studies with rat brain sodium channels) |
| Gating modifiers | α-Scorpion toxins and sea anemone toxins, which probably slow inactivation based on studies with peripheral nerves and Nav1.28,9 |
| Blockers | Nonselective: tetrodotoxin (EC50 = 4 nM in rat,2 25 nM in human3), saxitoxin; local anesthetic, antiepileptic, and antiarrhythmic drugs (lidocaine EC50 = 450 μM in resting state at –100 mV10) |
| Radioligands | [125I]α-scorpion toxin, [3H]batrachotoxin, [3H]saxitoxin [3H]tetrodotoxin (based on studies with rat brain sodium channels) |
| Channel distribution | All types of DRG neurons, sympathetic neurons, Schwann cells, and neuroendocrine cells2,3,11 |
| Physiological functions | Action potential initiation and transmission in peripheral neurons; slow closed-state inactivation facilitates response to slow, small depolarizations12 |
| Mutations and pathophysiology | Mutations (I848T and I858H), observed in inherited erythromelalgia, negatively shift activation, slow deactivation, and enhance response to small depolarizations13,14 |
| Pharmacological significance | Probable target of local anesthetics in the peripheral nervous system |
aa, amino acids; chr., chromosome; TTX, tetrodotoxin; DRG, dorsal root ganglion; HEK, human embryonic kidney.
↵1. Toledo-Aral JJ, Moss BL, He Z-J, Koszowski G, Whisenand T, Levinson SR, Wolf JJ, Silos-Santiago I, Halegoua S, and 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
↵2. Sangameswaran L, Fish LM, Koch BD, Rabert DK, Delgado SG, Ilnikca M, Jakeman LB, Novakovic S, Wong K, Sze P, et al. (1997) A novel tetrodotoxin-sensitive, voltage-gated sodium channel expressed in rat and human dorsal root ganglia. J Biol Chem 272:14805-14809
↵3. Klugbauer N, Lacinova L, Flockerzi V, and Hofmann F (1995) Structure and functional expression of a new member of the tetrodotoxin-sensitive voltage-activated sodium channel family from human neuroendocrine cells. EMBO J 14:1084-1090
↵4. Belcher SM, Zerillo CA, Levenson R, Ritchie JM, and Howe JR (1995) Cloning of a sodium channel α subunit from rabbit Schwann cells. Proc Natl Acad Sci USA 92:11034-11038
↵5. Beckers M-C, Ernst E, Belcher S, Howe J, Levenson R, and Gros P (1996) A new sodium channel α-subunit gene (Scn9a) from Schwann cells maps to the Scn1a, Scn2a, Scn3a cluster of mouse chromosome 2. Genomics 36:202-205
↵6. Kozak CA and Sangameswaran L (1996) Genetic mapping of the peripheral sodium channel genes, Scn9a and Scn10a, in the mouse. Mamm Genome 7:787-792
↵7. Rush AM, Bräu ME, Elliott AA, and Elliott JR (1998) Electrophysiological properties of sodium current subtypes in small cells from adult rat dorsal root ganglia. J Physiol (Lond) 511:771-789
↵8. 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
↵9. 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
↵10. Chevrier P, Vijayaragavan K, and Chahine M (2004) Differential modulation of Nav1.7 and Nav1.8 peripheral nerve sodium channels by the local anesthetic lidocaine. Br J Pharmacol 142:576-584
↵11. Felts PA, Yokoyama S, Dib-Hajj S, Black JA, and Waxman SG (1997) Sodium channel α-subunit mRNAs I, II, III, NaG, Na6 and hNE (PN1): different expression patterns in developing rat nervous system. Mol Brain Res 45:71-82
↵12. Cummins TR, Howe JR, and Waxman SG (1998) Slow closed-state inactivation: a novel mechanism underlying ramp currents in cells expressing the hNE/PN1 sodium channel. J Neurosci 18:9607-9617
↵13. Yang Y, Wang Y, Li S, Xu Z, Li H, Ma I, Fan J, Bu D, Liu B, Fan Z, et al. (2004) Mutations in SCN9A, encoding a sodium channel alpha subunit, in patients with primary erythermalgia. J Med Genetics 41:171-174
↵14. Cummins TR, Dib-Hajj SD, and Waxman SG (2004) Electrophysiological properties of mutant NaV1.7 sodium channels in a painful inherited neuropathy. J Neurosci 24:8232-8236