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

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概要

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• A variety of different isoforms of voltage-sensitive Na+ channels have now been identified. The recent three-dimensional analysis of Na+ channels has unveiled a unique and unexpected structure of the Na+ channel protein. Na+ channels can be classified into two categories on the basis of their amino acid sequence, NaV1 isoforms currently comprising nine highly homologous clones and NaX that possesses structure diverging from NaV1, especially in several critical functional motifs. Although the functional role of NaV1 isoforms is primarily to form an action potential upstroke in excitable cells, recent biophysical studies indicate that some of the NaV1 isoforms can also influence subthreshold electrical activity through persistent or resurgent Na+ currents. NaV1.8 and NaV1.9 contain an amino acid sequence common to tetrodotoxin resistant Na+ channels and are localized in peripheral nociceptors. Recent patch-clamp experiments on dorsal root ganglion neurons from NaV1.8-knock-out mice unveiled an additional tetrodotoxin-resistant Na+ current. The demonstration of its dependence on NaV1.9 provides evidence for a specialized role of NaV1.9, together with NaV1.8, in pain sensation. Although NaX 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+ channels are reviewed, to give a perspective for future research on the expanding family of Na+ channel clones.

• 社団法人 日本薬理学会の論文
• 2002-04-01

著者

• Ogata Nobukuni

  Department Of Neurophysiology Graduate School Of Biomedical Sciences Hiroshima University

• OHISHI Yoshiaki

  Department of Physiology, Hiroshima University School of Medicine

• Ohishi Yoshiaki

  Department Of Physiology Hiroshima University School Of Medicine

• Ogata Nobuyuki

  Department of Neurophysiology, Graduate School of Biomedical Sciences, Hiroshima University

• Ohishi Yoshiaki

  Department of Neurophysiology, Graduate School of Biomedical Sciences, Hiroshima University

関連論文

• Involvement of Voltage-Gated Sodium Channel Na_v1.8 in the Regulation of the Release and Synthesis of Substance P in Adult Mouse Dorsal Root Ganglion Neurons
• Prostaglandin E_2 Has No Effect on Two Components of Tetrodotoxin-Resistant Na^+ Current in Mouse Dorsal Root Ganglion
• Use-Dependent Removal of the 4-Aminopyridine-Induced Block of the Transient K^+ Current in Rat Dorsal Root Ganglia
• The role of Tetrodotoxin-resistant Sodium Channels Pain Sensation
• REVIEW Molecular Diversity of Structure and Function of the Voltage-Gated Na^+ Channels
• EFFECTS OF PENICILLIN ON ELECTRICAL ACTIVITIES OF NEURONS IN GUINEA-PIG HIPPOCAMPAL SLICES
• Prostaglandin E2 Has No Effect on Two Components of Tetrodotoxin-Resistant Na+ Current in Mouse Dorsal Root Ganglion

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