Structure and Function of Sodium Channel Nav1.3 in Neurological Disorders.

ABSTRACT

Nav1.3, encoded by the SCN3A gene, is a voltage-gated sodium channel on the cell membrane. It is expressed abundantly in the fetal brain but little in the normal adult brain. It is involved in the generation and conduction of action potentials in excitable cells. Nav1.3 plays an important role in many neurological diseases. The aim of this review is to summarize new findings about Nav1.3 in the field of neurology. Many mutations of SCN3A can lead to neuronal hyperexcitability and then cause epilepsy. The rapid recovery from inactivation and slow closed-state inactivation kinetics of Nav1.3 leads to a reduced activation threshold of the channel and a high frequency of firing of neurons. Hyperactivity of Nav1.3 also induces increased excitability of sensory neurons, a lower nociceptive threshold, and neuropathic pain. This review summarizes the structure and the function of Nav1.3 and focuses on its relationship with epilepsy and neuropathic pain.