1997 Fiscal Year Final Research Report Summary
NEUROMUSCULAR DISEASES CAUSED BY ABANORMAL EXCITATION-CONTRACTION COUPLING
| Project/Area Number |
08670742
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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 |
Neurology
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| Research Institution | OKINAKA MEMORIAL INSTITUTE FOR MEDICAL RESEARCH(OMIMR) |
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Principal Investigator |
TAKAGI Akio OMIMR,CHIEF RESEARCHER,OKINAKA MEMORIAL INSSTITUTE FOR MEDICAL RESEARCH, 研究員 (20010142)
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| Co-Investigator(Kenkyū-buntansha) |
上坂 義和 (財)冲中記念成人病研究所, 研究員
IDA Masayoshi OMIMR,RESEARCHER,OKINAKA MEMORIAL INSTITUTE FOR MEDICAL RESEARCH, 研究員
WATANABE Tomoji OMIMR,RESEARCHER,OKINAKA MEMORIAL INSTITUTE FOR MEDICAL RESEARCH, 研究員
KOJIMA Susumu OMIMR,RESEARCHER,OKINAKA MEMORILA INSTITUTE FOR MEDICAL RESEARCH, 研究員
NAKASE Hirohumi OMIMR,RESEARCHER,OKINAKA MEMORIAL INSTITUTE FOR MEDICAL RESEARCH, 研究員 (80155738)
UESAKA Kazuyoshi OMIMR,RESEARCHER,OKINAKA MEMORIAL INSTITUTE FOR MEDICAL RESEARCH
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| Project Period (FY) |
1996 – 1997
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| Keywords | MALIGNANT HYPERTHERMIA / CENTRAL CORE DISEASE / RYANODINE RECEPTOR / CALCIUM ION / CAFFEINE / MUTATION |
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| Research Abstract |
Malignanthyperthermia(MH)is a serious complication of general anesthesia, presenting high fever, tachyarrhithmia, acidosis and myoglobinuria. MH is a heterogeneous disorder, but half of MH cases are associated with various mutation of ryanodine receptor gene of the skeletal muscle(ryr1). Central core disease(CCD), a form of congenital myopathy, frequently developed MH.In some of CCD cases, mutation of ryr1 is also reported. In the first part, we studied pharmacological aspects of caffeine to supplement the caffeine contracture test.
Using theskinned muscle fiber preparation, influence of caffeine on the muscle fiber was compared between mdx and control mouse. Tension generataion was depressed by 30mM caffeine in high calcium ion(Ca)such as-pCa4.5. In type 2 muscle fibers of mdx, increase of tension by caffeine was always more marked than in controls. On the other hand, influence of caffeine ontype 1 fiber was the same between mdx and control. Reasons for this difference between type 1 and 2 is not clear yet.
In familial patients with CCD,who had recovered from episode of MH,contracture by caffeine was markedly exaggerated. In a case of the postoperative MH,caffeine response was abnormal only in the type 2 fiber. In twocaseswith suspected MH,results of caffeine contracture were equivocal. On thefamily with CCD,complicated with MH,all the known mutation of ryr1 was not detected.
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