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

我们建立了ryanodine受体2型（RyR-2(+/-)）敲除小鼠，并探讨了心脏的功能。Langenforff灌注时，我们未发现K.O.小鼠心脏压力（dP/dt、-dP/dt）和舒张末期容积有明显变化。我们得出结论，RyR-2的部分缺失得到了很好的补偿。然后，我们重点研究了在[Ca^<2+>]i的调控中起重要作用的肌浆网Ca^<2+>泵（SERCA2a）。我们过表达SERCA 2a （TG）并探讨其心脏功能。TG组p /dt和dp /dt均大于非TG组（NTG）。在TG中，当心脏承受较高的压力时，心肌肥厚明显减轻。因此，SERCA2a在改善病理生理适应中起着关键作用。我们解剖了左心室的乳头肌，用aequorin测量了Ca^<2+>瞬态（CaT）。CaT的峰值大于NTG。TG组CaT病程较NTG组快。在NTG中，异丙肾上腺素增加了CaT的峰值，缩短了CaT的时间过程。然而，在TO组中，这些参数没有明显变化。CO_2酸中毒时，NTG的CaT升高，收缩减少。在TO中，观察到类似的变化，但对酸中毒收缩的抑制减弱。收缩恢复也比NTG好。因此，SERCA2a在病理生理条件下起着举足轻重的作用。

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.