Chaudhri Babar, Del Monte Federica, Hajjar Roger J, Harding Sian E
National Heart and Lung Institute, Faculty of Medicine, Imperial College of Science, Technology and Medicine, London SW3 6LY, United Kingdom.
Am J Physiol Heart Circ Physiol. 2002 Dec;283(6):H2450-7. doi: 10.1152/ajpheart.00391.2002. Epub 2002 Aug 8.
Sarco(endo)plasmic reticulum Ca(2+)-ATPase (SERCA)2a overexpression and phospholamban depletion have been shown to have beneficial effects on contractility in heart failure. However, the high sympathetic tone during development of failure may interact with increases in SERCA2a activity in potentially deleterious ways. We used adenoviral vectors to overexpress SERCA2a or partially downregulate phospholamban in adult rabbit ventricular myocytes in culture and studied the responses of these cells to beta-adrenoceptor stimulation. SERCA2a overexpression and phospholamban depletion had quantitatively similar effects on basal contraction amplitude and in accelerating relaxation. Increasing SERCA2a activity by either strategy had little effect on the increase in contraction amplitude or incidence of arrhythmias with increasing isoproterenol. Maximum acceleration of relaxation by beta-adrenoceptor stimulation was similar to that produced by SERCA2a overexpression. Isoproterenol treatment of SERCA2a-overexpressing or phospholamban-deficient myocytes produced a further modest decrease in relaxation time, with similar final values in both groups. We find no evidence for Ca(2+) overload induced by SERCA2a overexpression alone or in combination with catecholamines.
肌质（内质）网Ca(2+) -ATP酶（SERCA）2a的过表达和受磷蛋白的缺失已被证明对心力衰竭时的心肌收缩力有有益影响。然而，在心力衰竭发展过程中高交感神经张力可能以潜在有害的方式与SERCA2a活性增加相互作用。我们使用腺病毒载体在培养的成年兔心室肌细胞中过表达SERCA2a或部分下调受磷蛋白，并研究这些细胞对β -肾上腺素能受体刺激的反应。SERCA2a过表达和受磷蛋白缺失对基础收缩幅度和加速舒张具有数量上相似的影响。通过这两种策略增加SERCA2a活性对异丙肾上腺素浓度增加时收缩幅度的增加或心律失常的发生率影响很小。β -肾上腺素能受体刺激引起的舒张最大加速与SERCA2a过表达产生的相似。用异丙肾上腺素处理过表达SERCA2a或缺乏受磷蛋白的心肌细胞会使舒张时间进一步适度缩短，两组的最终值相似。我们没有发现单独的SERCA2a过表达或与儿茶酚胺联合使用会导致Ca(2+)过载的证据。
