Description: sodium channel, voltage-gated, type X, alpha subunit
Gene: Scn10a     Synonyms: nav1.8, scn10a

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The gene SCN10A (also known as PN3; SNS; hPN3; Nav1.8) encodes the voltage-gated sodium channel alpha subunit, type X, Na1.8. SCN10A encodes a TTX-resistant channel that is restricted to the peripheral sensory nervous system [854]. Nav1.8 is found only within small-diameter sensory neurons in the periphery generating electrical impulses and transmiting nociceptive information to the central nervous system in cold temperatures, unlike the other sodium channels which have enhanced slow inactivation with cooling [1430].



RGD ID Chromosome Position Species
3629 8 124578222-124690458 Rat
736179 9 119517584-119603478 Mouse
1349086 3 38738837-38835501 Human

Scn10a : sodium channel, voltage-gated, type X, alpha subunit



Acc No Sequence Length Source
NM_017247 n/A n/A NCBI
NM_009134 n/A n/A NCBI
NM_006514 n/A n/A NCBI

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Nav1.8 channels interact with various commercially available compounds such as menthol, lidocaine, tetracaine, vinpocetine, ambroxol, lamotrigine, mexilitine, veratridine, and A-803467, whereas very few animal toxins have been shown to be capable of reshaping Nav1.8 currents [1429]. For example, lidocaine, suppresses Na+ currents by binding not only to DIV–S6 but also to S6 of DI and DII, blocking the channels in a use-dependent (frequency-dependent) and voltage-dependent manner [856], [857]. Lidocaine enhanced current decrease in a frequency-dependent manner. Steady-state inactivation of Nav1.8 and Nav1.7 channels was also affected by lidocaine, Nav1.7 being the most sensitive. Only the steady-state activation of Nav1.8 was affected while the entry of both channels into slow inactivation was affected by lidocaine, Nav1.8 being affected to a larger degree. [217]

Beta subunits [220]

Nav1.8 is likely to be co-expressed with the b1, b2, and b3-subunits in C-fiber neurons from the DRG, and these subunits interact and modulate the channel.

  • b1-subunit alone, or in combination with other b-subunits, accelerates the time constant of inactivation and shifts the voltage-dependence of activation to more hyperpolarized potentials. Beta-1 also increases levels of Nav1.8 channel functional expression, either by increasing channel density at the oocyte membrane or by increasing individual channel conductance.

  • b3-subunit shifts the voltage-dependence of inactivation to more positive potentials and do not influence the time constant of current decay, steadystate activation or expression of Nav1.8. Co-expression of b1 and b3-subunits with Nav1.8 resulted in little change in availability compared to channel alone.

  • b2-subunit do not alter the kinetic properties or current amplitude of However, the co-expression of b1 and b2 shift the Nav1.8 channel availability to more depolarized potentials in comparison to when channels are expressed with either b1 or b2 alone.

Other proteins that interact with Nav1.8 [1431]

p11 directly binds only to NaV1.8 and translocate it to the plasma membrane.

PDZD2 and syntrophin-associated serine/threonine kinase (SASTK) are linked to the functional expression of NaV1.8 on the plasma membrane.

Contactin regulates the surface expression of Nav1.8.

CAP-1A binds to a conserved motif present in NaV1.8 linking voltage-gated sodium channels to clathrin, which is involved in coated vesicle assembly.


Nav1.8 is TTX resistant [1376]



The a-subunit - such as Nav1.8 - is composed of four homologous domains (DI–DIV), each of which is composed of six transmembrane segments (S1–S6).

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Nav1.8 is expressed both in the soma of IB4+ and IB4- cells [859] and in the axons [1437] of the dorsal root glanlia. It has been also expressed in the somas located of the rat trigemina ganglia [859].

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The channel is expressed only by small-diameter sensory neurons in neonatal and adult dorsal root and trigeminal ganglia [854]. Nociceptive dorsal root ganglion (DRG) neurons can be classified into nonpeptidergic IB4+ and peptidergic IB4- subtypes, which terminate in different layers in dorsal horn and transmit pain along different ascending pathways, and display different firing properties. Voltage-gated, tetrodotoxin-resistant (TTX-R) Nav1.8 channels are expressed in both IB4+ and IB4- cells and produce most of the current underlying the depolarizing phase of action potential (AP). use-dependent reduction of Nav1.8 current in IB4+ neurons is significantly stronger than that in IB4- neurons, although voltage dependency of activation and steady-state inactivation are not different.[218]
Nav1.8 is detected in unmyelinated fibers innervating cornea [1452] and it has been reported at 20% of nodes of Ranvier in myelinated axons that innervate tooth pulp [1453].

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The Nav1.8 channel is able to reactivate rapidly and can still sending action potentials to the central nervous systemeven when other channels remain desensitized [1433].


Gain-of-function changes caused by mutations increase the excitability of DRG neurons. These observations suggest that Nav1.8 mutations contribute to pain in some peripheral neuropathies :
* Visceral pain [1434]
* Cold pain [1430]
* Mechanical and inflammatory pain [1435]
Nav1.8, together with Nav1.7, accumulates in painful human neuromas and is responsible for ectopic axonal hyper excitability, resulting in abnormal sensory phenomena such as pain and paresthesias [858].

Mouse models:
- Nav1.8 null [1436]
- Nav1.7/Nav1.8 double KO [1427], [1428]

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Nav1.8 produces a slowly inactivating sodium current characterized by depolarized voltage dependency [859], [860] and rapid recovery from fast inactivation [861], [862], [863]. Nav1.8 channels produce the majority of the inward current during the AP upstroke in the DRG neurons in which they are present [846], [865], most of which are nociceptive [866]. TTX-R currents attributable to Nav1.8 enter rapidly into, and recover slowly from, slow inactivation even during short depolarizing pulses from holding potentials near resting membrane potential, thereby contributing to adaptation of firing in response to capsaicin application [867]. (This summary is from [218])



Browne LE et al. Functional and pharmacological properties of human and rat NaV1.8 channels.
Neuropharmacology, 2009 Apr , 56 (905-14).


Vijayaragavan K et al. Role of auxiliary beta1-, beta2-, and beta3-subunits and their interaction with Na(v)1.8 voltage-gated sodium channel.
Biochem. Biophys. Res. Commun., 2004 Jun 25 , 319 (531-40).


Vijayaragavan K et al. Gating properties of Na(v)1.7 and Na(v)1.8 peripheral nerve sodium channels.
J. Neurosci., 2001 Oct 15 , 21 (7909-18).


Ragsdale DS et al. Molecular determinants of state-dependent block of Na+ channels by local anesthetics.
Science, 1994 Sep 16 , 265 (1724-8).


Renganathan M et al. Contribution of Na(v)1.8 sodium channels to action potential electrogenesis in DRG neurons.
J. Neurophysiol., 2001 Aug , 86 (629-40).

Gilchrist J et al. Animal toxins can alter the function of Nav1.8 and Nav1.9.
Toxins (Basel), 2012 Aug , 4 (620-32).

Zimmermann K et al. Sensory neuron sodium channel Nav1.8 is essential for pain at low temperatures.
Nature, 2007 Jun 14 , 447 (855-8).

Swanwick RS et al. The trafficking of Na(V)1.8.
Neurosci. Lett., 2010 Dec 10 , 486 (78-83).

Faber CG et al. Gain-of-function Nav1.8 mutations in painful neuropathy.
Proc. Natl. Acad. Sci. U.S.A., 2012 Nov 20 , 109 (19444-9).

Abrahamsen B et al. The cell and molecular basis of mechanical, cold, and inflammatory pain.
Science, 2008 Aug 1 , 321 (702-5).

Nassar MA et al. Nociceptor-specific gene deletion reveals a major role for Nav1.7 (PN1) in acute and inflammatory pain.
Proc. Natl. Acad. Sci. U.S.A., 2004 Aug 24 , 101 (12706-11).



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