1993 Fiscal Year Final Research Report Summary
A correlative study of myocardial relaxation, intracellular Ca^<2+> concentration, expression of the sarcoplasmic reticulum Ca^<2+>-ATPase.
| Project/Area Number |
03670440
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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 | University of Tokyo |
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Principal Investigator |
MOMOMURA Shin-ichi Univ.of Tokyo, Faculty of Medicine, Assistant Pro, 医学部(病), 助手 (10190985)
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| Co-Investigator(Kenkyū-buntansha) |
KINUGAWA Koh-ichiro Univ.of Tokyo, Faculty of Medicine, Medical Fellow, 医学部(病), 医員
TAKAHASHI Toshiyuki Univ.of Tokyo, Faculty of Medicine, Lecturer, 医学部(病), 助手 (40236302)
SERIZAWA Takashi Univ.of Tokyo, Faculty of Medicine, Lecturer, 医学部(病), 講師 (90143429)
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| Project Period (FY) |
1991 – 1993
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| Keywords | Cardiac myocyte / Myocardial hypertrophy / Myocardial relaxation / Intracellular Ca^<2+>-handling / Sarcoplasmic reticulum Ca^<2+>-ATPase / Na^+ / Ca^<2+> exchanger / RNA blot analysis |
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| Research Abstract |
Intracellular Ca^<2+>-hadling has been reported to be altered along with myocardial hypertrophy. To well characterize the altered Ca^<2+>-handling in hypertrophied cardiac myocytes, an in vitro model of myocardial hypertrophy was created in cultured chick embryo (10-day-old) ventricular myocytes by exposure to 10% fetal calf serum (FCS) for 24 hours. In the FCS-treated group, both RNA and protein contents increased by about 25% as compared with the untreated control group (p<0.05, n=4), without any changes in cell number. The peak systolic [Ca^<2+>]_i (measured with indo-1) was lower (753<plus-minus>103 vs. 950<plus-minus>142 ms, p<0.050, n=4) and T_<1/2> of the decay of the Ca^<2+> transients was longer (163<plus-minus>7 vs.132<plus-minus>12 msec, p<0.05, n=4) in the FCS-treated group than in the control group. Thapsigargin (1 mM), an inhibitor of the sarcoplasmic reticulm (SR) Ca^<2+>-ATPase, induced a decrease in the peak systolic [Ca^<2+>]_i with an elongation of the T_<1/2> as obs
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erved in the FCS-treated group. RNA blot analysis revealed that the relative abundance of mRNA (determined by laser densitometry) encoding the SR Ca^<2+>-ATPase was decreased significantly (41.8<plus-minus>3.8% of the control group, p<0.05, n=4) in the FCS-treated group. The levels of Na^+/Ca^<2+> exchanger mRNA were also diminished in the FCS-treated group (35.0<plus-minus>4.3% of the control, p<0.05, n=4). Steady-state levels of [Ca^<2+>]_i during perfusion with Na^+-free solution including 10 mM caffeine (ONa+Caf), which blocks Na^+/Ca^<2+> exchanger and SR,was lower in the FCS-treated group (338<plus-minus>30 vs. 806<plus-minus>129 nM,p<0.05, n=4). When verapamil (1 mM) perfusion was followed, these differences were diminished (294<plus-minus>33 vs. 282<plus-minus>35 nM,NS). Perfusion with ONa+Caf after pretreatment with 1 mM vanadate (used as an inhibitor of the sarcolemmal Ca^<2+>-ATPase) also showed similar results. On the other hand, pretreatment with verapamil caused no significant differences in the steady-state [Ca^<2+>]_i during perfusion with ONa+Caf between the FCS-treated and control groups. These data suggest that the alterations in Ca^<2+>-handling occur along with cellular hypertrophy in our in vitro model. These changes in Ca^<2+>-handling may include down regulation of voltage-dependent Ca^<2+> channel as well as the SR Ca^<2+>-ATPase and Na^+/Ca^<2+> exchanger. Less
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[Publications] Kinugawa K,Takahashi T,Kohmoto O,Yao A,Momomura S,Serizawa T.: "Altered Ca^<2+>-handling during cellular hypertrophy in cultured chick ventricular myocytes.In The Asapted Heart.Nagano M,Takeda N,Dhalla NS,editors." Raven Press,New York(in press),
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