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