Scn10a is a tetrodotoxin-resistant voltage-gated sodium channel alpha subunit. Epithelial sodium channels are amiloride-sensitive members of the Degenerin/epithelial sodium channel (Deg/ENaC) superfamily of ion channels. Scn10a mediates the voltage-dependent sodium ion permeability of excitable membranes. Assuming opened or closed conformations in response to the voltage difference across the membrane, Scn10a forms a sodium-selective channel through which sodium ions may pass in accordance with their electrochemical gradient. Scn10a also plays a role in neuropathic pain mechanisms. Structurally, members of Deg/ENaC superfamily of ion channels share organizational similarity in that they all possess two short intracellular amino and carboxyl termini, two short membrane spanning segments, and a large extracellular loop with a conserved cysteine-rich region. There are three homologous isoforms of the ENaC (alpha, beta, and gamma) protein. ENaC in the kidney, lung, and colon plays an essential role in trans-epithelial sodium and fluid balance. ENaC also mediates aldosterone-dependent sodium reabsorption in the distal nephron of the kidney, thus regulating blood pressure. ENaC is thought to be regulated, in part, through association with the cystic fibrosis transmembrane conductance regulator (CFTR) chloride ion channel. Gain-of-function mutations in beta- or gamma-ENaC can cause severe arterial hypertension (Liddels syndrome) and loss-of-function mutations in alpha- or beta-ENaC causes pseudohypoaldosteronism (PHA-1). Diseases associated with SCN10A include Episodic Pain Syndrome, Familial, 2 and Sodium Channelopathy-Related Small Fiber Neuropathy.
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Protein Aliases: mPN3; Peripheral nerve sodium channel 3; PN3; Sensory neuron sodium channel; Sodium channel protein type 10 subunit alpha; Sodium channel protein type X subunit alpha; sodium channel type X alpha polypeptide; sodium channel voltage-gated type X alpha polypeptide; sodium channel, voltage gated, type X alpha subunit; sodium channel, voltage-gated, type 10, alpha polypeptide; sodium channel, voltage-gated, type X, alpha polypeptide; sodium channel, voltage-gated, type X, alpha subunit; voltage gated sodium channel; Voltage-gated sodium channel subunit alpha Nav1.8
Gene Aliases: FEPS2; hPN3; Na(V)1.8; Nav1.8; PN3; SCN10A; SNS
Molecular Function: voltage-gated ion channel