2000 Fiscal Year Final Research Report Summary
Study on ion transport of cardiac Na^+-K^+ pump and Na^+-Ca^<2+> exchnage
| Project/Area Number |
11670041
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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 |
General physiology
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| Research Institution | KYOTO UNIVERSITY |
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Principal Investigator |
MATSUOKA Satoshi Kyoto University, Graduate School of Medicine, Research associate, 医学研究科, 助手 (00263096)
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| Project Period (FY) |
1999 – 2000
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| Keywords | Na / Ca exchange / Na pump / Heart / Stoichiometry / Simulation |
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| Research Abstract |
1. We successfully developed a method to excise macro-patch from intact cardiac ventricular cells and recorded Na^+-Ca^<2+> exchange (I_<Na/Ca>) and Na^+-K^+ pump currents (cardiac cell macro-patch method).
2. We studied stoichiometry of Na^+-Ca^<2+> exchange using the cardiac cell macro-patch method by determining reversal potentials of I_<Na/Ca>. The stoichiometry was approximately 4Na^+ : 1Ca^<2+>, which was different from currently-accepted 3Na^+ : 1Ca^<2+>. It was suggested that the stoichiometry gets close to 3Na^+ : 1Ca^<2+> as cytoplasmic Na^+ decreases to less than 5 mM.
3. We studied regulation by cytoplasmic Na^+ and Ca^<2+> of I_<Na/Ca> in the macro-patch. Kinetics of Na^+ dependent inactivation was about two-fold faster than the exchanger in blebs and the one expressed in oocytes. Ca^<2+> activation was about ten times faster. We proposed that the Ca^<2+> regulation functions in a beat-to-beat manner in beating cells.
4. We developed a mathematical Na^+-Ca^<2+> exchange model
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, based on the macro-patch data. The model can well simulate Na^+ and Ca^<2+> dependences, the Na^+ dependent inactivation and the activation by Ca^<2+>.
5. We studied contribution of Na^+-Ca^<2+> exchange in a beating heart cell by computer simulation. At resting membrane potential, the majority of Na^+-Ca^<2+> exchange was in inactive states and does not function. The exchanger returns to the active state as intracellular Ca^<2+> transient occurs and functions in a forward mode. The exchanger enters the inactive states as intracellular Ca^<2+> concentration declines.
6. In voltage-clamped ventricular cells, we successfully recorded charge movement associated with the Na^+ translocation of Na^+-K^+ pump by a rapid extracellular Na^+ concentration jump. Charge movement associated with the Ca^<2+> translocation could also be recorded by an extracellular K^+ jump. The total charge of K^+ translocation was about 1/4 of the one of Na^+ translocation. It was indicated that the K^+ translocation step is voltage sensitive as well as Na^+ translocation step. Less
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[Publications] Nakamura, E., Sato, M., Yang, H., Miyagawa, F., Harasaki, M., Tomita, K., Matsuoka, S., Noma, A., Iwai, K., and Minato, N.: "4F2 (CD98) heavy chain is associated covalently with an amino acid transporter and controls intracellular trafficking and membrane topology of 4F2 heterodimer."Journal of Biological Chemistry. 274. 3009-3016 (1999)
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[Publications] Matsuoka, S., Fujioka, Y.& Noma, A.: "Regulation and stoichiometry of Na^+-Ca^<2+> exchange in inside-out macro patch excised from intact guinea-pig ventricular cells."Ccontrol and diseases of sodium dependent transport proteins and ion channels. Edited by Suketa, Y., Carafoli, E., Lazdunski, M., Mikoshiba, K., Okada, Y.and Wright, E.M.. Elsevier. (2000)
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「研究成果報告書概要(欧文)」より
