2003 Fiscal Year Final Research Report Summary
Intracellular Ca^<2+> regulation in the myocardium with ryanodine receptor type 2(+/-) heterozygous mouse
| Project/Area Number |
13670048
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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 | Jikei University School of Medicine |
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Principal Investigator |
KURIHARA Satoshi Jikei University, School of Medicine, Professor, 医学部, 教授 (90057026)
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| Co-Investigator(Kenkyū-buntansha) |
OTSU Kinya Osaka University, Graduate School of Medicine Dept.of Internal Medicine and Therapeutics, Research Assistant, 医学系研究科・医学部, 助手 (20294051)
KUSAKARI Yoichiro Jikei University, School of Medicine, Research Assistant, 医学部, 助手 (80338889)
HONGO Kenichi Jikei University, School of Medicine, Lecturer, 医学部, 講師 (00256447)
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| Project Period (FY) |
2001 – 2003
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| Keywords | intracellular Ca^<2+> / myocardium / ryanodine receptor type2 / mouse / SERCA2a / Ca^<2+> transient / isoprenaline / acidosis |
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| Research Abstract |
We produced knockout mouse with ryanodine receptor type 2 (RyR-2(+/-)) and explored the cardiac functions of the heart. In Langenforff perfusion, we could not detect any significant changes of the parameters of pressure (dP/dt, -dP/dt) and end diastolic volume in the heart in K.O. mouse. We concluded that the partial deletion of RyR-2 is well compensated. Then, we focused on the Ca^<2+> pump of sarcoplasmic reteiculum (SERCA2a) which plays an important role in the regulation of [Ca^<2+>]i. We overexpressed SERCA 2a (TG) and explored its cardiac functions. In TG, &P/dt and-dP/dt were larger than those in nonTG (NTG). In TG, cardiac hypertrophy was significantly reduced when the heart was loaded with higher pressure. Thus, SERCA2a plays a key role to improve pathophysiological adaptation. We dissected papillary muscles from the left ventricle of TO and measured Ca^<2+> transient(CaT) with aequorin. The peak of CaT was larger than that of NTG. The time courses of CaT in TG were faster than those in NTG. In NTG, isoprenaline increased the peak of CaT and shortened the time course of CaT. However, no significant changes of these parameters were observed in TO. In CO_2 acidosis, contraction was decreased although CaT was increased in NTG. In TO, similar changes were observed but the inhibition of contraction in acidosis was reduced. The recovery of contraction was also better than that in NTG. Thus, SERCA2a plays a pivotal role under pathophysiological condition.
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