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