Investigation of the effect of CACNA1S mutation on intracellular calcium kinetics

2021 Fiscal Year Final Research Report

• Project/Area Number: 20K17813
• Research Category: Grant-in-Aid for Early-Career Scientists
• Allocation Type: Multi-year Fund
• Review Section: Basic Section 55050:Anesthesiology-related
• Research Institution: Hiroshima University
• Principal Investigator: Otsuki Sachiko 広島大学, 医系科学研究科(医), 助教 (90774018)
• Project Period (FY): 2020-04-01 – 2022-03-31
• Keywords: 悪性高熱症 / カルシウム拮抗薬

Outline of Final Research Achievements

Malignant hyperthermia is a lethal complication of general anesthesia caused by abnormally elevated calcium concentration in skeletal muscle cells. We investigated the intracellular calcium kinetics of nifedipine, a calcium antagonist. We planned to compare the response with CACNA1S and RYR1 mutations, the genes responsible for malignant hyperthermia. However, since only one cell type with the CACNA1S mutation could be measured, the results were compared with and without a predisposition to malignant hyperthermia.
The 50% effective concentration of nifedipine was 0.79±0.20 μM in those with a predisposition to malignant hyperthermia (n=10) and 1.32±0.15 μM in those without (n=5)(p=0.0013).
Intracellular calcium concentrations were more elevated in skeletal muscle predisposed to malignant hyperthermia.

Free Research Field

麻酔

Academic Significance and Societal Importance of the Research Achievements

ニフェジピンは悪性高熱素因者の骨格筋で優位に細胞内カルシウム濃度を上昇させ、高濃度のニフェジピンでは筋小胞体からのカルシウム漏出が続くことが分かった。このことから、悪性高熱症の素因者では、健常者と比較し、ニフェジピンにより細胞内カルシウム濃度が上昇しやすい可能性が考えられるが、臨床的な血中濃度の範囲内では問題になることはあまりないと考えられた。