NaV1.9 channels

Channel name NaV1.9
Description Voltage-gated sodium channel α subunit
Other names NaN, SNS-2
Molecular information human: 1792aa, Q9UHE0, AF188679, chr. 3p21-3p24, SCN11A
Rat: 1765aa, 088457, NM_019265, AJ237852,
Mouse: 1765aa, Q9R053, NM_011887, chr. 9
Associated subunits Not established
Functional assays Voltage clamp
Current INaTTX-RP
Conductance Not established
Ion selectivity Na+
Activation Threshold = —70 to —60 mV (rat DRG), —80mV (human)
Va = —47 to —54 mV (rat DRG)1,2,3; τa = 2.93 ms at —60 mV, 4.1 ms at —50 mV, 3.5 ms at —20 mV, and 2.5 ms at —10 mV3
Inactivation Vh = —44 to —54 mV1,3; τh = 843 ms at —60 mV, 460 ms at —50 mV, 43 ms at —20 mV, and 16 ms at —10 mV3
Activators Not established
Gating modifiers Not established
Blockers Tetrodotoxin (TTX-resistant, EC50 = 40 mM)
Radioligands None
Channel distribution c-type DRG neurones, trigeminal neurones and their axons; preferentially expressed in nociceptive DRG neurons4
Physiological functions Contributes a depolarizing influence to resting potential, amplifies slow subthreshold depolarizations1,3 and modulates excitability of cell membrane5
Mutations and pathophysiology Preferential expression in c-type dorsal root ganglion neurons suggests a role in nociception
Pharmacological significance Potential target for analgesic drugs
Comments Expression is regulated by GDNF6; NaV1.9 current is increased by inflammatory mediators such as PGE27
  • aa, amino acids; chr., chromosome; DRG, dorsal root ganglion; TTX, tetrodotoxin; GDNF, glial cell-derived growth factor; PG, prostaglandin.

  • 1. Cummins TR, Dib-Hajj SD, Black JA, Akopian AN, Wood JN, and Waxman SG (1999) A novel persistent tetrodotoxin-resistant sodium current in SNS-null and wild-type small primary sensory neurons. J Neurosci 19:RC43

  • 2. Sleeper AA, Cummins TR, Hormuzdiar W, Tyrrell L, Dib-Hajj SD, Waxman SG, and Black JA (2000) Changes in expression of two tetrodotoxin-resistant sodium channels and their currents in dorsal root ganglion neurons following sciatic nerve injury, but not rhizotomy. J Neurosci 20:7279-7289

  • 3. Herzog RI, Cummins TR, and Waxman SG (2001) Persistent TTX-resistant Na+ current affects resting potential and response to depolarization in simulated spinal sensory neurons. J Neurophysiol 86:1351-1364

  • 4. Fang X, Djouri L, Black JA, Dib-Hajj SD, Waxman SG, and Lawson SN (2002) The presence and role of the TTX-resistant sodium channel NaV1.9 in nociceptive primary afferent neurons. J Neurosci 22:7425-7434

  • 5. Baker MD, Chandra SY, Ding Y, Waxman SG, and Wood JN (2003) GTP-induced tetrodotoxin-resistant Na current regulates excitability in mouse and rat small diameter sensory neurones. J Physiol (Lond) 548:373-382

  • 6. Cummins TR, Black JA, Dib-Hajj SD, and Waxman SG (2000) GDNF up-regulates expression of functional SNS and NaN sodium channels and their currents in axotomized DRG neurons. J Neurosci 20:8754-8761

  • 7. Rush AM and Waxman SG (2004) PGE2 increases the tetrodotoxin-resistant NaV1.9 sodium current in mouse DRG neurons via G-proteins. Brain Res 1023:264-271