Immunochistochemical distribution of voltage gated sodium channel subunits in mouse brain

NEUROSCIENCE RESEARCH(2011)

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摘要
This chapter summarizes developments within the voltage-gated sodium channel (VGSC) field focusing on the structural classes. The nine VGSCs (NaV1.1–1.9) discovered to date are members of a larger voltage-gated ion channel super-family which regulates the electrical activity among cells and tissues, and is involved in many physiological processes such as cognition, locomotion, and nociception. Of the nine VGSCs, NaV1.1, NaV1.2, NaV1.3, and NaV1.6 are distributed throughout the central nervous system (CNS). NaV1.4 is present in muscle tissue, and NaV1.5 is in cardiac myocytes, while NaV1.7, NaV1.8, and NaV1.9 are distributed in the peripheral nervous system (PNS). It is now known, however, that the expression of VGSCs can change significantly under pathological conditions such as neuropathic pain or multiple sclerosis (MS). For example, NaV1.8 mRNA and protein are up-regulated within cerebellar purkinje cells in animal models of MS and in human MS conditions. Similarly, mRNA for NaV1.8 is down-regulated in the dorsal root ganglia (DRG) but up-regulated in undamaged neurons in both rodent models of neuropathic pain and in human chronic pain conditions. The attention derived from the recent genetic studies of loss-of-function mutations of SCN9A (NaV1.7) in man has propelled these targets to the forefront of drug discovery.
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voltage gated sodium channel
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