Nav1.8

Nav1.8

Diagram of the alpha subunit structure of Nav1.8

Nav1.8, also known as sodium channel, voltage-gated, type X, alpha subunit (SCN10A), is a voltage-gated sodium channel that is primarily expressed in peripheral neurons. It plays a crucial role in the generation and conduction of action potentials in nociceptive neurons, which are responsible for the sensation of pain.

Structure

Nav1.8 is composed of an alpha subunit that forms the pore of the channel. The alpha subunit is a large transmembrane protein that consists of four homologous domains (I-IV), each containing six transmembrane segments (S1-S6). The S4 segment acts as the voltage sensor, while the S5 and S6 segments form the pore through which sodium ions pass. The intracellular loops between the domains are important for channel gating and modulation.

Function

Nav1.8 is unique among sodium channels due to its resistance to tetrodotoxin (TTX), a potent sodium channel blocker. This property allows Nav1.8 to continue functioning in conditions where other sodium channels are inhibited. Nav1.8 is activated at more depolarized membrane potentials compared to other sodium channels, which makes it particularly important in the transmission of pain signals under pathological conditions.

Expression

Nav1.8 is predominantly expressed in small-diameter dorsal root ganglion (DRG) neurons and trigeminal ganglion neurons. These neurons are involved in the transmission of nociceptive information from the periphery to the central nervous system. The expression of Nav1.8 can be upregulated in response to nerve injury or inflammation, contributing to chronic pain states.

Clinical Significance

Mutations in the SCN10A gene, which encodes the Nav1.8 channel, have been associated with various pain disorders. Gain-of-function mutations can lead to increased pain sensitivity, while loss-of-function mutations may result in reduced pain perception. Nav1.8 is a target for the development of new analgesic drugs aimed at treating chronic pain conditions without affecting normal sensory functions.

Related Pages

• Voltage-gated sodium channel
• Nociception
• Dorsal root ganglion
• Chronic pain