Intracellular Ca^<2+> regulation in the myocardium with ryanodine receptor type 2(+/-) heterozygous mouse

兰尼定受体2型(/-)杂合小鼠心肌细胞内Ca^<2>调节

基本信息

批准号：
13670048
负责人：
KURIHARA Satoshi
金额：
$ 2.18万
依托单位：
Jikei University School of Medicine
依托单位国家：
日本
项目类别：
Grant-in-Aid for Scientific Research (C)
财政年份：
2001
资助国家：
日本
起止时间：
2001 至 2003
项目状态：
已结题

项目摘要

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.

我们制作了兰尼碱受体2型（RyR-2（+/-））基因敲除小鼠，并探索了心脏的心脏功能。在 Langenforff 灌注中，我们无法检测到 K.O. 心脏压力参数（dP/dt、-dP/dt）和舒张末期容积的任何显着变化。老鼠。我们得出结论，RyR-2 的部分缺失得到了很好的补偿。然后，我们重点关注了肌浆网Ca^2+泵(SERCA2a)，它在[Ca^2+]i的调节中发挥着重要作用。我们过表达 SERCA 2a (TG) 并探索其心脏功能。在TG中，&P/dt和-dP/dt大于非TG(NTG)中的那些。在TG中，当心脏负荷较高的压力时，心脏肥大显着减少。因此，SERCA2a 在改善病理生理适应方面发挥着关键作用。我们从TO的左心室解剖乳头肌并用水母发光蛋白测量Ca 2+ 瞬态(CaT)。 CaT 的峰比 NTG 的峰大。 TG中CaT的时程比NTG中的要快。在NTG中，异丙肾上腺素增加了CaT的峰值并缩短了CaT的时程。然而，在 TO 中没有观察到这些参数的显着变化。在CO_2酸中毒中，尽管NTG中CaT增加，但收缩减少。在TO中，观察到类似的变化，但酸中毒时收缩的抑制减弱。收缩恢复也比NTG好。因此，SERCA2a在病理生理条件下发挥着关键作用。