| Project/Area Number |
15591083
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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 |
Pediatrics
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| Research Institution | Akita University |
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Principal Investigator |
SAWAISHI Yukio Akita University, School of Medicine, Research Associate, 医学部, 講師 (90250894)
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| Co-Investigator(Kenkyū-buntansha) |
SUZUKI Akira Akita University, School of Medicine, Professor, 医学部, 教授 (10311565)
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| Project Period (FY) |
2003 – 2004
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| Project Status |
Completed (Fiscal Year 2004)
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| Budget Amount *help |
¥3,700,000 (Direct Cost: ¥3,700,000)
Fiscal Year 2004: ¥1,400,000 (Direct Cost: ¥1,400,000)
Fiscal Year 2003: ¥2,300,000 (Direct Cost: ¥2,300,000)
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| Keywords | sodium channel / lidocaine / epilepsy / モデルマウス |
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| Research Abstract |
We have previously reported a case of early infantile status epilepticus characterized by continual epileptic seizures with electroencephalogram patterns of long suppression with intermittent short burst activity. All the clinico-electrical findings consistently improved by lidocaine at a low serum concentration (10^<-6> M). Here we identify a de novo missence mutation (I1473M) of SCN2A gene just proximal to the III-IV linker. Patch-clamp analysis of the orthologous mutation of rat Na_v1.2 (rNa_v1.2) show negative shift of steady-state inactivation curve and slowing of recovery from fast inactivation, resulting in decreased channel availability. High concentration of lidocaine (0.5 mM) induces tonic block and use-dependent block with a similar magnitude between wild-type and I1473M mutant rNa_v1.2 channels. The low concentration of lidocaine (10^<-8> to 10^<-6> M), by contrast, shifts the steady-state activation curve towards the negative potentials and increases current amplitude at negative potentials in the mutant channels but not in the wild-type channels, when they are coexpressed with the auxiliary β subunit. The findings indicate that lidocaine effects lead not only to decrease in sodium channel currents but also to increase under certain circumstances.
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