SCN3A

SCN3A is a gene that encodes the alpha subunit of the voltage-gated sodium channel Nav1.3. This channel is primarily expressed in the central nervous system and plays a crucial role in the initiation and propagation of action potentials in neurons. Mutations in the SCN3A gene have been associated with a variety of neurological disorders, including epilepsy, migraine, and autism spectrum disorder.

Structure

The SCN3A gene is located on the short arm of chromosome 2 (2q24.3) and spans approximately 200 kilobases. It consists of 26 exons that encode a protein of 2000 amino acids. The Nav1.3 channel is composed of four homologous domains (I-IV), each containing six transmembrane segments (S1-S6). The S4 segment in each domain acts as the voltage sensor, while the pore-forming loop between S5 and S6 is responsible for sodium ion selectivity and conductance.

Function

The Nav1.3 channel is a critical component of the neuronal excitability machinery. It is responsible for the rapid influx of sodium ions into the neuron, which depolarizes the membrane and initiates the action potential. The channel is also involved in the regulation of neurotransmitter release and synaptic plasticity.

Clinical significance

Mutations in the SCN3A gene can lead to a variety of neurological disorders. For example, gain-of-function mutations can cause familial hemiplegic migraine type 3 (FHM3), a severe form of migraine characterized by hemiplegia (paralysis on one side of the body) during the aura phase. Loss-of-function mutations, on the other hand, can result in epilepsy and autism spectrum disorder. In addition, recent studies have suggested a potential role of SCN3A in the pathogenesis of Alzheimer's disease.

See also

• Voltage-gated sodium channel
• Neuronal excitability
• Action potential
• Epilepsy
• Migraine
• Autism spectrum disorder

References

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