2002 Fiscal Year Final Research Report Summary
Molecular analysis of the neuropathic pain state using sns-null mutant mice
| Project/Area Number |
13470313
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| Research Category |
Grant-in-Aid for Scientific Research (B)
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| Allocation Type | Single-year Grants |
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| Section | 一般 |
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| Research Field |
Orthopaedic surgery
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| Research Institution | HIROSHIMA UNIVERSITY |
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Principal Investigator |
FUJIMOTO Yoshinori Hiroshima University, Graduate School of Biomedical Sciences, Associate Professor, 大学院・医歯薬学総合研究科, 助教授 (30199377)
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| Co-Investigator(Kenkyū-buntansha) |
OGATA 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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| Project Period (FY) |
2001 – 2002
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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_<Na>s. 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_<Na>s : one is resistant to tetrodotoxin (TTX) and found exclusively in small DRG neurons (I_<TTX-R/persist>), and the otner 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 Na_V1.9, while the latter may be mediated by Na_V1.6. To confirm these possibilities, we performed single cell nested RT-PCR combined with concurrent patch clamp recording and investigated the correlation between mRNA
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expression and phenotype of I_<Na> in an identified DRG neuron. I_<TTX-R/persist> was recorded in isolation from small DRG neurons of Na_V1.8-null mutant mice in the presence of TTX. Most of the small neurons, which were associated with Na_V1.9 transcript, manifested I_<TTX-R/persist>, confirming that the isoform mediating I_<TTX-R/persist> is probably Na_V1.9. Unexpectedly, however, Na_V1.9 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 Na_V1.9 transcript. An intriguing finding was that Na_V1.9 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 Na_V1.6 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 by Na_V1.6. Less
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Research Products
(11 results)
