Functional role of the voltage-gated sodium charnel in chronic pain state
| Project/Area Number |
18613008
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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 |
Pain science
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| Research Institution | Hiroshima University |
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Principal Investigator |
OGATA Nobukuni Hiroshima University, Gradiate School of Biomedical Sciences, Professor (80091255)
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| Project Period (FY) |
2006 – 2007
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| Project Status |
Completed (Fiscal Year 2007)
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| Budget Amount *help |
¥3,830,000 (Direct Cost: ¥3,500,000、Indirect Cost: ¥330,000)
Fiscal Year 2007: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000)
Fiscal Year 2006: ¥2,400,000 (Direct Cost: ¥2,400,000)
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| Keywords | chronic pain / sodium channel / primary sensory neuron |
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| Research Abstract |
Small dorsal root ganglion neurons express preferentially the Na^+ channel isoform Na_γ1.9 that mediates a tetrodotoxin-resistant (TIX-R) Na^+ current. We investigated properties of the Na^+ current mediated by Na_γ1.9 (I_<NN>) using the whole-cell, patch-clamp recording technique. To isolate I_<NN> from heterogeneous TIX-R Na^+ currents that also contain another type of TIX-R Na^+ current mediated by Na_γ1.8, we used Na_γ1.8-null mutant mice. When F was used as an internal anion in the patch pipette solution, both the activation and inactivation kinetics for I_<NN> shifted in the hyperpolarizing direction with time. Such a time-dependent shift of the kinetics was not observed when Cl^- was used as an internal anion. Functional expression. Of I_<NN> declined with time after cell dissociation and recovered during culture, implying that Na_γ1.9 may be regulated dynamically by trophic factors or depend on subtle environmental factors for its survival. During whole-cell recordings, the peak amplitude of INaN increased dramatically after a variable delay, as if inactive or silent channels had been "kindled". Such an unusual increase of the amplitude could.be prevented by adding AIP to the pipette solution or by recording with the nystatin-perforated patch-clamp technique, suggesting that the rupture of patch membrane affected the behaviour of NaV1.9. These peculiar properties of INaN may provide an insight into the plasticity of Na^+ charnels that are related to pathological functions of Na^+ channels accompanying abnormal pain states.
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Report
(3 results)
Research Products
(13 results)
