View source for Sodium Channelopathies

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Voltage gated sodium channels are transmembrane polypeptides with four domains. A pore is made with all four domains through which sodium can enter the cell. There is also an ancillary beta unit for anchoring and kinetics. They are responsible for signalling the nerve fibres for generation of action potentials (See also [[Basic Neurophysiology]] and [[Channelopathies and Chronic Pain]]). 

== Classification ==
There are nine known members of sodium channels labelled Na<sub>v</sub>1.1 through Na<sub>v</sub>1.9. The associated genes are named SCN1A through SCN11A (the SCN6/7A gene is part of the Na<sub>x</sub> sub-family and has uncertain function)
{| class="wikitable"
|+'''Table 1.''' Nomenclature and some functions of voltage-gated sodium channel alpha subunits<ref>{{Cite journal|date=2022-12-02|title=Sodium channel|url=https://en.wikipedia.org/w/index.php?title=Sodium_channel&oldid=1125082712|journal=Wikipedia|language=en}}</ref>
!Protein name
!Gene
!Expression profile
!Associated channelopathies
|-
!Na<sub>v</sub>1.1
|''SCN1A''
|Central neurons, [peripheral neurons] and cardiac myocytes
|febrile epilepsy, GEFS+, Dravet syndrome (also known as ''severe myclonic epilepsy of infancy'' or SMEI), borderline SMEI (SMEB), West syndrome (also known as ''infantile spasms''), Doose syndrome (also known as ''myoclonic astatic epilepsy''), intractable childhood epilepsy with generalized tonic-clonic seizures (ICEGTC), Panayiotopoulos syndrome, familial hemiplegic migraine (FHM), familial autism, Rasmussens's encephalitis and Lennox-Gastaut syndrome
|-
!Na<sub>v</sub>1.2
|''SCN2A''
|Central neurons, peripheral neurons
|inherited febrile seizures, epilepsy, and autism spectrum disorder
|-
!Na<sub>v</sub>1.3
|''SCN3A''
|Central neurons, peripheral neurons and cardiac myocytes
|epilepsy, pain, brain malformations, ?[[Trigeminal Neuralgia|trigeminal neuralgia]]
|-
!Na<sub>v</sub>1.4
|''SCN4A''
|Skeletal muscle
|Certain non-dystrophic [[Myotonia|myotonias]]: Sodium channel myotonia, Paramyotonia congenita, Hyperkalaemic periodic paralysis
|-
!Na<sub>v</sub>1.5
|''SCN5A''
|Cardiac myocytes, uninnervated skeletal muscle, central neurons, gastrointestinal smooth muscle cells and Interstitial cells of Cajal
|Cardiac: Long QT syndrome Type 3, Brugada syndrome, progressive cardiac conduction disease, familial atrial fibrillation and idiopathic ventricular fibrillation;
Gastrointestinal: Irritable bowel syndrome;
|-
!Na<sub>v</sub>1.6
|''SCN8A''
|Central neurons, dorsal root ganglia, peripheral neurons, heart, glia cells
|Epilepsy,  ataxia, dystonia, tremor
|-
!Na<sub>v</sub>1.7
|''SCN9A''
|Dorsal root ganglia, sympathetic neurons, Schwann cells, and neuroendocrine cells
|'''Gain of function''': SCN9A neuropathic pain syndromes: [[erythromelalgia]],[[Small Fibre Neuropathy|Small fibre neuropathy]], paroxysmal extreme pain disorder

'''Loss of function''': Congenital Insensitivity to Pain (CIP) a.k.a hereditary sensory and autonomic neuropathy type 2D (HSAN2D)
|-
!Na<sub>v</sub>1.8
|''SCN10A''
|Dorsal root ganglia
|[[Small Fibre Neuropathy|Small fibre neuropathy]], [[Familial Episodic Pain Syndrome|familial episodic pain syndrome type 2]], autosomal recessive neuromuscular disease and epileptic encephalopathy, Brugada syndrome, and congenital abnormalities of the kidney and urinary tract.
|-
!Na<sub>v</sub>1.9
|''SCN11A''
|Dorsal root ganglia
|[[Small Fibre Neuropathy|Small fibre neuropathy]], [[Familial Episodic Pain Syndrome|familial episodic pain syndrome type 3]], autosomal dominant hereditary sensory and autonomic neuropathy type 7 (HSAN7)
|-
!Na<sub>x</sub>
|''SCN7A''
|heart, uterus, skeletal muscle, astrocytes, dorsal root ganglion cells
|none known
|}

== Clinical Features ==

=== Primary (SCN9A) Erythromelalgia ===
[[Erythromelalgia|Primary Erythromelalgia]] is characterized by recurrent, bilateral episodes of intense burning pain, redness, warmth, and sometimes swelling, SCN9A-EM most commonly affects the feet. However, severely affected individuals may also experience involvement of the hands, legs, arms, face, and/or ears.

=== Paroxysmal Extreme Pain Disorder ===
[[Paroxysmal Extreme Pain Disorder]] typically begins during infancy or the neonatal period and includes autonomic symptoms such as skin flushing, patchy or asymmetric colour changes (harlequin), non-epileptic tonic attacks (stiffening), and fainting accompanied by a slow heart rate (syncope with bradycardia). Later manifestations involve severe, deep burning pain in the rectal, ocular, or submandibular regions, along with erythematous skin changes (flushing).

=== Inherited Small Fibre Neuropathy ===
[[Small Fibre Neuropathy]] is an adult-onset condition marked by neuropathic pain in a stocking and glove distribution, often described as burning. Autonomic symptoms may include dry eyes and mouth, orthostatic dizziness, palpitations, and bowel or bladder disturbances. Large nerve fiber functions, such as normal strength, tendon reflexes, and vibration sense, are preserved.

== See Also ==
[https://www.ncbi.nlm.nih.gov/books/NBK1163/ GeneReviews - SCN9A Pain Conditions]

== References ==
[[Category:Physiology]]
<references />
{{Reliable sources}}
[[Category:Genetic Disorders]]