2002 Fiscal Year Final Research Report Summary
Molecular mechanism of neuropathic pain aberrant expression of voltage-gated sodium and potassium channels
| Project/Area Number |
11680753
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| Research Category |
Grant-in-Aid for Scientific Research (C)
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| Allocation Type | Single-year Grants |
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| Section | 一般 |
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| Research Field |
Neurochemistry/Neuropharmacology
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| Research Institution | Kanazawa University |
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Principal Investigator |
YOKOYAMA Shigeru Kanazawa University Graduate School of Medicine, Department of Biophysical Genetics, Associate Professor, 大学院・医学系研究科, 助教授 (00210633)
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| Co-Investigator(Kenkyū-buntansha) |
HIGASHIDA Haruhiro Kanazawa University Graduate School of Medicine, Department of Biophysical Genetics, Professor, 大学院・医学系研究科, 教授 (30093066)
HOSHI Naoto Kanazawa University Graduate School of Medicine, Department of Biophysical Genetics, Research Associate, 大学院・医学系研究科, 助手 (90229170)
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| Project Period (FY) |
1999 – 2002
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| Keywords | voltage-gated potassium channel / Kv1.1 / Kv1.2 |
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| Research Abstract |
Kv1.1 and Kv1.2, two most closely related members of the Shaker-like gene subfamily, encode pore-forming subuaits of voltage-gated potassium (K^+) channels. To clarify physiological roles of these proteins in primary sensory afferentiation, we have performed inimunohistochemical analysis using specific antidodies. Immunoperoxidase staining of dorsal root and trigeminal ganglia revealed that strong immunoreactivity (IR) for Kv1.1 and Kv1.2 was predominant in medium- and large-sized neurons. In double-immunofluorescence experiments, the cells strongly positive for these subunits were most frequently observed in RT97 (neurofilament)-positive large neurons; but rarely in peripherin- or IB4-positive small neurons. In the spinal dorsal horn, both the aati-Kv1.1 and anti-Kv1.2 antibodies heavily staiaed the deeper laminae III-IV. At the electron microscopic level, IRs for these proteins were preferentially localized in myelinated axons with large diameter. These results suggest that voltage-gated K^+ channels composed of Kv 1.1 and/or Kv 1.2 subunits may play important roles in conducting mechanoceptive and proprioceptiye sensation from skin and muscles. Conceivably, decreased expression of these channels after injury might cause hypereexcitability of neurons, thereby leading to hyperalgegia or allodyaia.
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[Publications] Macica, C. M., von Hehn, C. A. A., Yang-Wang, L., Ho, C. S., Yokoyama, S., Joho, R. H., and Kaczmarek, L. K.: "Modulation of the Kv3.1b potassium channel isoform adjusts the fidelity of the firing pattern of auditory neurons."J. Neurosci.. 23. 1133-1141 (2003)
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