| Project/Area Number |
03044114
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| Research Category |
Grant-in-Aid for international Scientific Research
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| Allocation Type | Single-year Grants |
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| Section | Joint Research |
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| Research Institution | KYUSHU UNIVERSITY |
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Principal Investigator |
NOMA Akinori Kyushu University, Faculty of Medicine, 医学部, 教授 (00132738)
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| Co-Investigator(Kenkyū-buntansha) |
ROLAND Kozlowski University of Oxford, University Laboratory of Physiology, 生理学研究所, 助手
TREVOR Powell University of Oxford, University Laboratory of Physiology, 生理学研究所, 教授
ONO Kyoichi Kyushu University, Faculty of Medicine, 医学部, 助手 (70185635)
KOZLOWSKI Ro オックスフォード大学, 生理学研究所, 助手
POWELL Trevo オックスフォード大学, 生理学研究所, 教授
光家 保 九州大学, 医学部, 講師 (40174065)
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| Project Period (FY) |
1991 – 1992
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| Project Status |
Completed (Fiscal Year 1992)
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| Budget Amount *help |
¥5,500,000 (Direct Cost: ¥5,500,000)
Fiscal Year 1992: ¥2,000,000 (Direct Cost: ¥2,000,000)
Fiscal Year 1991: ¥3,500,000 (Direct Cost: ¥3,500,000)
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| Keywords | Cadiac Muscle / Ca Flux / Cytosolic Ca / Ca Channel / Na-Ca Exchanger / Caged Ca / Whole Cell Clamp / Turnover Rate / 回転率 / 細胞内Ca濃度 / 細胞膜電流 / イオン輸送 |
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| Research Abstract |
The regulation of the cytosolic Ca^<2+> concentration is a essential process to maintain the cellular function in every type of cells. In the cardiac myocytes the influx of Ca^<2+> is conducted mainly through the Voltage-gated Ca^<2+> channel, and the efflux via the Na^+-Ca^<2+> exchanger. Namely, the depolarization of the action potential opens the L-type Ca^<2+> channels, which triggers the contraction of the muscle. During the diastole, the Na^+-Ca^<2+> exchange pump out the Ca^<2+> using the electrochemical driving force for Na^+. Under various types of pathological conditions, pumping out of Ca^<2+> is disturbed, so that the cell become overloaded with Ca^<2+>. To investigate the function of the Na^+-Ca^<2+> exchanger, we measured the membrane current, which is produced by the Na^+-Ca^<2+> exchanger (the Na^+-Ca^<2+> exchange current), simultaneously with the measurement of the intracellular free Ca^<2+>. The single ventricular myocytes were obtained by treating the guinea-pig hea
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rt with collagenase, and its membrane currents were measured using the whole cell patch clamp technique. The Ca^<2+>-indicator, Indo-1 was loaded within the cell through the whole cell patch clamp electrode. It was found that the depolarization of the membrane increased the amplitude of the outward Na^+-Ca^<2+> exchange current, and simultaneously the intracellular Ca^<2+> concentration increased. The integration of the Na^+-Ca^<2+> exchange current well corresponded to the increase of the intracellular Ca^<2+> concentration. In a separate series of experiments, the cytosolic Ca^<2+> concentration was raised instantaneously using the photolabile compound, Nitr-5. The flash photolysis of this caged Ca^<2+> activated the inward Na^+-Ca^<2+> exchange current in a single exponential time course. This finding is consistent with an Na^+-Ca^<2+> exchange model having the electrogenic step in the Na^+ transporting step. Based on the conventional exchanger model, we conclude that the turnover rate is at least 125 s^<-1> at 26 ﾟC -80 mv, and the site density is more than 2000/ mu m^2. Less
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