|Recommended name:||Sodium channel protein type 9 subunit alpha|
|Sequence length:||1988 AA.|
|Drug Bank:||Sodium Channel|
Voltage-gated sodium channels are activated through an action potential firing.
There are nine pore-forming α-subunits (Nav1.1 - Nav1.9) known in mammals. Each α-subunit consists of four repeat domains each containing six membrane-spanning segments. These subunits interact with β-subunits and other proteins. Since Nav1.7, Nav1.8 and Nav1.9 are mainly expressed in peripheral neurons, it is possible to target them without affecting the central nervous system or heart. Especially Nav1.7 was found to play an important role in acute and inflammatory pain.
Voltage-gated sodium channels represent the target for local anesthetic agents. It is challenging to find selective targets of sodium channels in the pain pathway. Genotyping of families suffering from congenital indifference to pain identified mutations in gene coding for Nav1.7 channels. Other subtypes of voltage-gated sodium channels (Nav1.3, Nav1.8, Nav1.9) play also important roles, but to date it is difficult to develop subtype-specific sodium-channel blocking agents.
Nav1.7 is important for the perception of pain. Mutations in the SCN9A gene showed several effects on the expression of the α-subunit. Patients without Nav1.7 showed insensitivity to pain. People suffering from erythromelalgia have a mutation of the SCN9A gene, which - in contrast - leads to extremely high Nav1.7-activity. This causes attacks of burning pain and elevated skin temperature.