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SCN10A : ウィキペディア英語版
Nav1.8

Nav1.8 is a sodium ion channel that in humans is encoded by the ''SCN10A'' gene.〔(【引用サイトリンク】 url = http://www.ncbi.nlm.nih.gov/sites/entrez?Db=gene&Cmd=ShowDetailView&TermToSearch=6336 )〕 Nav1.8 is a sodium channel subunit.
Nav1.8 is a tetrodotoxin (TTX)-resistant voltage-gated sodium ion channel. It is expressed specifically in the dorsal root ganglion (DRG), in unmyelinated, small-diameter sensory neurons called C-fibres and is involved in the pain pathway called nociception.〔
〕〔
〕 C-fibres can be activated by noxious thermal or mechanical stimuli and thus can carry pain messages.
The discrete locations of Nav1.8 in sensory neurons of the DRG may be the key factor in therapeutic targets for the development of new analgesics and to treat chronic pain.〔

==Function==

Voltage-gated sodium ion channels (VGSC) are essential in producing and propagating action potentials. Tetrodotoxin, a toxin found in pufferfish is able to block some VGSCs and therefore is used to distinguish the different subtypes. There are three TTX-resistant VGSC: Nav1.5, Nav1.8 and Nav1.9. Nav1.8 and Nav1.9 are both expressed in nociceptors (damage-sensing neurons). It is known that Nav1.7, Nav1.8 and Nav1.9 are located in the DRG and play an important role in maintaining chronic inflammatory pain.〔


Nav1.8 α-subunit consists of four homologous domains each with six transmembrane spanning regions of which one is a voltage sensor. Voltage clamp methods were used to show how action potentials in small diameter DRG cell bodies are shaped by TTX-resistant sodium channels. Nav1.8 contributes the most to sustaining the depolarising stage of the action potentials in nociceptive sensory neurons by activating quickly and remaining activated〔
〕〔
〕 after detecting a noxious stimulus.
Therefore, Nav1.8 is known to perform a key role in hyperalgesia (increased sensitivity to pain) and allodynia (pain from stimuli that do not usually cause it) which are part of chronic pain.〔
〕 Nav1.8 knockout mice studies have shown that the channel is associated with inflammatory and neuropathic pain.〔〔
〕〔
〕 Moreover, Nav1.8 plays a crucial role in cold pain.〔
〕 Zimmermann ''et al.'' show that reducing the temperature from 30 °C to 10 °C slows the activation of VGSCs and hence decreases the current. However, Nav1.8 is cold-resistant and is able to generate action potentials in the cold to carry information from nociceptors to the central nervous system (CNS). Furthermore, Nav1.8-null mice failed to produce action potentials therefore indicating Nav1.8 is essential in the notion of pain in cold temperatures.〔

抄文引用元・出典: フリー百科事典『 ウィキペディア(Wikipedia)
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