心筋細胞のエネルギー代謝におけるミトコンドリアと筋小胞体Ca<sup>2+</sup>放出チャネルの相対位置の重要性

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  • Juxtaposition of Mitochondria to the Ca<sup>2+</sup> Release Site is Crucial for the Cardiac Energy Balance—A 3-D Simulation Study of Cardiomyocyte—
  • 心筋細胞のエネルギー代謝におけるミトコンドリアと筋小胞体Ca²⁺放出チャネルの相対位置の重要性
  • シンキン サイボウ ノ エネルギー タイシャ ニ オケル ミトコンドリア ト キン ショウホウタイ Ca ² ⁺ ホウシュツ チャネル ノ ソウタイ イチ ノ ジュウヨウセイ

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Recent studies revealed that Ca2+not only regulates the contraction of cardiomyocytes, but can also function as a signal to stimulate ATP production by the mitochondria. However, spatio-temporal resolutions of current experimental techniques limit our understanding on this issue. This study employs our 3D cardiomyocyte model based on the finite element method (Okada et al. AJP 2005) and has been extended to include the detailed subcellular structure including the sarcolemma with t-tubule system, sarcoplasmic reticulum, myofibrils and mitochondria. Elementary processes involved in the electrophysiology, contraction and ATP metabolism are spatially arranged, and the multiple reaction diffusion equations for Ca2+and energy metabolites, and contraction were solved simultaneously. We specifically examined the effect of the gap distance between mitochondria and Ca2+release site. Our model revealed that increasing the gap distance induced a severe energetic derangement due to phosphate accumulation, resulting in contractile failure under tachycardic electrical pacing at 3Hz. Juxtaposition of the mitochondria to the Ca2+release site is crucial for rapid signal transmission to maintain cardiac energy balance. Realistic 3-D model of cardiac excitation-contraction and metabolism provides a powerful tool for the study of cardiac function by expanding the temporal and spatial resolution beyond the limit in experimental approaches.

収録刊行物

  • 生体医工学

    生体医工学 49 (6), 829-835, 2011

    公益社団法人 日本生体医工学会

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