1999 Fiscal Year Final Research Report Summary
Pharmacological research on CaィイD12+ィエD1 channel abnormality which induces epileptic seizures.
| Project/Area Number |
09470024
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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 |
General pharmacology
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| Research Institution | Hiroshima University |
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Principal Investigator |
SASA Masashi Hiroshima University, Faculty of Medicine, Professor, 医学部, 教授 (20025654)
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| Co-Investigator(Kenkyū-buntansha) |
SERIKAWA Tadao Kyoto University, Faculty of Medicine, Professor, 医学研究科, 教授 (30025655)
MATSUBAYASHI Hiroaki Hiroshima University, Faculty of Medicine, Assistant Professor, 医学部, 講師 (60165850)
ISHIHARA Kumatoshi Hiroshima University, Faculty of Medicine, Associate Professor, 医学部, 助教授 (20212912)
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| Project Period (FY) |
1997 – 1999
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| Keywords | CaィイD12+ィエD1 channel / fura / hippocampal CA3 / calcium influx / aspartpacetylase / nifedipine / spontaneously epileptic rat (SER) / tm gene |
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| Research Abstract |
The following studies were performed to elucidate the function of CaィイD12+ィエD1. channels which induce epileptic seizures in spontaneously epileptic rat (SER: tm/tm, zi/zi).
1. Search for the gene to induce epileptic seizures in SER :
The tm gene was found to locate in the area between D10M11Mit351 and D10M11Mit7 on the chromosome 10 and delate approximately 200KB between the areas. The aspartoacetylase gene, the enzyme for metabolizing N-acetyl-L-aspartate (NAA) was found to be included within the deletion. Actually NAA level was increased in the brain and intra cerebroventricular injection of NAA induced absence-like seizures accompanying with 5-10Hz spike-wave complexes in cortical and hippocampal EEG in the normal wistar rat and the premature tremor rat, which is parent strain for SER and exhibits absence-like seizures before the age with the seizures. NAA also induced depolarization shift and repetitive firing in hippocampal CA3 of the normal wistar rat.
2. Enhancement of CaィイD12+ィエD1 influxes in SER hippocampus :
In the hippocampal slice preparation of SER which is exhibiting the seizures. CaィイD12+ィエD1. influxes in CA3 area neurons with high K' under treatment with fura 2/AM were more pronounced than those in the normal rat.
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