THE MECHANISM OF ANTI-ARRHYTHMIC EFFECT OF Mg^<2+> UNDER Ca^<2+> OVERLOAD
| Project/Area Number |
04670528
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| Research Category |
Grant-in-Aid for General Scientific Research (C)
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| Allocation Type | Single-year Grants |
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| Research Field |
Circulatory organs internal medicine
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| Research Institution | HAMAMATSU UNIVERSITY SCHOOL OF MEDICINE |
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Principal Investigator |
KOBAYASHI Akira Hamamatsu Uni.Internal Med.Associate Professor, 医学部, 助教授 (00096588)
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| Co-Investigator(Kenkyū-buntansha) |
TERADA Hajime Hamamatsu Uni.Internal Med.Research Associate, 医学部, 助手 (50252177)
HAYASHI Hideharu Hamamatsu Uni.Photon Me.Res.Cen.Associate Professor, 光量子医学研究センター, 助教授 (50135258)
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| Project Period (FY) |
1992 – 1993
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| Project Status |
Completed (Fiscal Year 1993)
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| Budget Amount *help |
¥2,200,000 (Direct Cost: ¥2,200,000)
Fiscal Year 1993: ¥600,000 (Direct Cost: ¥600,000)
Fiscal Year 1992: ¥1,600,000 (Direct Cost: ¥1,600,000)
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| Keywords | MAGNESIUM / CALCIUM OVERLOAD / CALCIUM WAVES / ANTIARRHYTHMIC EFFECT / CALCIUM TRANSIENT / CAFFEINE / VERAPAMIL / TRIGGERED ACTIVITY / Ca^<2+>transient / Mgnesium / Calcium wave / Arrhythmia |
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| Research Abstract |
The arrythmias caused by Ca^<2+> overload have been suggested to be due to the triggered activities resulting from the spontaneous Ca^<2+> release from sarcoplasmic reticulum (SR). The phenomenon that the discrete region of elevated [Ca^<2+>]i travels along a myocyte is called the Ca^<2+> wave and is frequently observed under Ca^<2+> overloaded state. In this study, it was shown that raising the Mg^<2+> concentration of solution inhibited the Ca^<2+> wave with minimal suppression of electrically induced Ca^<2+> transient. The effect of Mg^<2+> was contrasted with the effect of verapamil, which inhibited the Ca^<2+> wave with the suppression of electrically induced Ca^<2+> transient. High Mg^<2+> solution also suppressed the Ca^<2+> wave in rested myocyte. These results suggested that the suppression of Ca^<2+> wave by Mg^<2+> was not related to the voltage dependent Ca^<2+> channel blocking property. To examine whether the effect of Mg^<2+> is exserted intracellulally, the effect of raising the Mg^<2+> concentration of solution on the [Mg^<2+>]i was examined. It was shown that raising the Mg^<2+> concentration increased the [Mg^<2+>]i with smilar time course to the suppression of Ca^<2+> wave. Since an increase in [Mg^<2+>]i has been reported to activate the Ca^<2+>-ATPase of SR and to inhibit Ca^<2+> releasing channel of SR, the amount of releasable Ca^<2+> in SR was estimated using post-rest and caffeine-induced C2+ transient as an index. Both post-rest and caffeine-induced Ca^<2+> transient were increased by high Mg^<2+> solution. These results suggested that antiarrythmic effect of Mg^<2+> is not due to the inhibition of voltage dependent Ca^<2+> channel, but due to an increase in Ca^<2+> holding capacity of SR.Since Mg^<2+> suppressed Ca^<2+> wave with minimal inhibition of electrically induced Ca<
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Report
(3 results)
Research Products
(11 results)
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[Publications] Noda, H., Hayashi, H., Miyata, H., Suzuki, S., Kobayashi, A., Yamazaki, N.: "Cytosolic Ca2+ concentration and pH of diabetic rat myocytes during metabolic inhibition." Molecular and Cellular Cardiology. 24(4). 435-446 (1992)
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[Publications] Hayashi, H., Miyata, H., Noda, N., Kobayashi, A., Hirano, M., Kawai, T., Yamazaki, N.: "Intracellular Ca2+ concentration and pHi during metabolic inhibition." Am.J.Physiol.262(Cell Physiology 31). C628-C634 (1992)
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[Publications] Terada, H., Noda, N., Satoh, H., Miyata, H., Kobayashi, A., Yamazaki, N., Hayashi, H.: "The mechanism of anti-arrhythmic effect of Mg2+ under Ca2+ overload - Effects of Mg2+ on "Ca2+ wave" and Ca2+ transients of rat ventricular myocytes.(in Japanese)" Therapeutic Res.14(2). 421-423 (1993)
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[Publications] Satoh, H., Hayashi, H., Noda, N., Terada, H., Kobayashi, A., Hirano, M., Yamashita, Y., Yamazaki, N.: "Regulation of [Na+]i and [Ca2+]i in guinea pig myocytes : dual loading of fluorescent indicators SBFI and fluo 3." Am.J.Physiol.266(Heart Circ.Physiol.35). H568-H576 (1994)
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