| Project/Area Number |
13670043
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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 |
General physiology
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| Research Institution | HIROSHIMA UNIVERSITY |
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Principal Investigator |
OGAT Nobukuni Hiroshima University, Graduate School of Biomedical Sciences, Professor, 大学院・医歯薬学総合研究科, 教授 (80091255)
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| Co-Investigator(Kenkyū-buntansha) |
OKAMURA yasushi National Institute of Advanced Industrial Science and Technology (AIST), Developmental neurobiology section, Team Leader, 生体機能制御研究室, 主任研究官
TERANISHI yasuhiro Hiroshima University, Graduate School of Biomedical Sciences, Associate Professor, 大学院・医歯薬学総合研究科, 助教授 (40112198)
宗重 博 広島大学, 医学部・附属病院, 助教授 (40211601)
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| Project Period (FY) |
2001 – 2002
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| Project Status |
Completed (Fiscal Year 2002)
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| Budget Amount *help |
¥3,300,000 (Direct Cost: ¥3,300,000)
Fiscal Year 2002: ¥1,200,000 (Direct Cost: ¥1,200,000)
Fiscal Year 2001: ¥2,100,000 (Direct Cost: ¥2,100,000)
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| Keywords | sodium channel / dorsal root ganglion / tetrodotoxin / channel conductance / voltage-clamp / patch-clamp |
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| Research Abstract |
Sensory neurons in dorsal root ganglia (DRG) express at least seven isoforms of voltage-gated sodium channel (VGSC) α-subunits. These isoforms show localized distribution within the primary sensory path-way and probably mediate multiple types of sodium currents (I-Na) with different kinetic properties, giving rise to fast, slow or persistent I-Nas. However, little is known as to which isoform is responsible for a particular I-Na in DRG neurons. We have recently identified two types persistent I-Nas: one is resistant to tetrodotoxin (TTX) and found exclusvely in small DRG neurons (I-TTX-R/persist),and theother is sensitive to TTX and found in medium / large DRG neurons (I-TTX-S / persist). Available data suggest that the former is most likely to be mediated by NaVl.9, while the latter may be mediated by NaV1.6. To confirm these possibilities, we performed single cell nested RT-PCR combined with concurrent patch clamp recording and investigated the correlation between mRNA expression and
… More
phenotype of I-NA in an identified DRG neuron. I-TTX-R / persist was recorded in isolation from small DRG neurons of NaV1.8-null mutant mice in the presence of TTX. Most of the small neurons, which were associated with NaV1.9 transcript, manifested I-TTX-R / persist, confirming that the isoform mediating I-TTX-R / persist is probably Nav1.9 Unexpectedly, however, Nav1.9 was evident also in a considerable number of medium / large neurons that were totally devoid of I-TTX-R / persist. These results indicate that I-TTX-R / persist is not solely dependent on the level of Nav1.9 transcript. An intriguing finding was that Nav1.9 transcript was often absent in small DRG neurons from naive mice while the same transcript was evident in most of the small DRG neurons from mutants. Expression of NaV1.6 transcript was demonstrated in a considerable portion of the medium / large neurons from both naive and mutant mice. However, these neurons did not consistently manifest I-TTX-S / persist suggesting that I-TTX-S / persist may not be carried b NaV1.6. Less
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