2000 Fiscal Year Final Research Report Summary
TITLE OF PROJECT : Effects of Drugs Used in Heart Failure on Energy Consumption of Loaded and Unloaded Cardiac Muscles.
| Project/Area Number |
10670098
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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 pharmacology
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| Research Institution | JUNTENDO UNIVERSITY |
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Principal Investigator |
KUREBAYASHI Kunihiro (呉林 なごみ) Juntendo Univ. Sch. Med. , Dept. Pharmacol. , Associate Professor, 医学部, 助教授 (50133335)
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| Project Period (FY) |
1998 – 2000
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| Keywords | heart / skinned fiber / ATPase / Energy consumption / heart failure / sarcoplasmic reticulum / Ca^<2+> |
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| Research Abstract |
1 To clarify the relative contribution of energy usage by contractile system, sarcoplasmic Ca^<2+> pump, and other source in loaded and unloaded cardiac muscles, we have measured and characterized ATPase activities and SR Ca^<2+> release property using skinned fibers from rat, guinea pig and canine ventricles and frog skeletal muscles. The properties of Ca^<2+> influx through plasma membrane in both types of muscles were also determined.
2 Actomyosin and basal Ca^<2+> -independent ATPase activities of rat ventricle were much higher than those of guinea pig. In contrast, SR Ca^<2+> ATPase activities were similar in fibers from both kinds of animals.
3 The affinities for Ca^<2+> and Mg^<2+> of the Ca^<2+> release channel in frog skeletal muscles were determined.
The results indicate that Ca^<2+> induced Ca^<2+> release (CICR) would not play an important role in frog skeletal muscles at physiological condition.
4 The CICR activity in cardiac muscle was more than 10 times higher than that in skeletal muscle. In addition, Ca^<2+> release activity was greatly enhanced under highly loaded condition of SR in cardiac muscle, which was not observed in skeletal muscle.
5 Ca^<2+> influx through plasma membrane was characterized. Store-operated Ca^<2+> influx (SOC) was observed in skeletal muscles. The possibility of contribution of SOC in cardiac muscle is under examination.
6 The results above suggest that Ca^<2+> regulating systems significantly affect energy consumption in cardiac muscles. We also found that a selection of experimental animal species is critically important in study of cardiac failure.
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[Publications] Nishi, M., Komazaki, S., Kurebayashi, N., Ogawa, Y., Noda, T., Iino, M.and Takeshima, H.: "Abnormal features in skeletal muscle from mice lacking Mitsugumin29."J.Cell Biol.. 147. 1473-80 (1999)
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