REVIEW Molecular Diversity of Structure and Function of the Voltage-Gated Na^+ Channels

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A variety of different isoforms of voltage-sensitive Na<sup>+</sup> channels have now been identified. The recent three-dimensional analysis of Na<sup>+</sup> channels has unveiled a unique and unexpected structure of the Na<sup>+</sup> channel protein. Na<sup>+</sup> channels can be classified into two categories on the basis of their amino acid sequence, Na<sub>V</sub>1 isoforms currently comprising nine highly homologous clones and Na<sub>X</sub> that possesses structure diverging from Na<sub>V</sub>1, especially in several critical functional motifs. Although the functional role of Na<sub>V</sub>1 isoforms is primarily to form an action potential upstroke in excitable cells, recent biophysical studies indicate that some of the Na<sub>V</sub>1 isoforms can also influence subthreshold electrical activity through persistent or resurgent Na<sup>+</sup> currents. Na<sub>V</sub>1.8 and Na<sub>V</sub>1.9 contain an amino acid sequence common to tetrodotoxin resistant Na<sup>+</sup> channels and are localized in peripheral nociceptors. Recent patch-clamp experiments on dorsal root ganglion neurons from Na<sub>V</sub>1.8-knock-out mice unveiled an additional tetrodotoxin-resistant Na<sup>+</sup> current. The demonstration of its dependence on Na<sub>V</sub>1.9 provides evidence for a specialized role of Na<sub>V</sub>1.9, together with Na<sub>V</sub>1.8, in pain sensation. Although Na<sub>X</sub> has not been successfully expressed in an exogenous system, recent investigations using relevant native tissues combined with gene-targeting have disclosed their unique "concentration"-sensitive but not voltage-sensitive roles. In this context, these emerging views of novel functions mediated by different types of Na<sup>+</sup> channels are reviewed, to give a perspective for future research on the expanding family of Na<sup>+</sup> channel clones.

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  • The Japanese journal of pharmacology

    The Japanese journal of pharmacology 88(4), 365-377, 2002-04-01

    The Japanese Pharmacological Society

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各種コード

  • NII論文ID(NAID)
    10008414863
  • NII書誌ID(NCID)
    AA00691188
  • 本文言語コード
    ENG
  • 資料種別
    REV
  • ISSN
    00215198
  • NDL 記事登録ID
    6263150
  • NDL 雑誌分類
    ZS51(科学技術--薬学)
  • NDL 請求記号
    Z53-D199
  • データ提供元
    CJP書誌  NDL  J-STAGE 
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