Analyses of the novel signal transduction mechanisms involved in the homeostasis of the intracellular calcium in the cardiovascular system.

磷蛋白是一种可逆的心肌肌浆网(SR)Ca^&lt；2-ATPase的抑制物，有助于调节心肌的收缩能力。由于只有单体形式的磷蛋白而不是五聚形式的磷蛋白抑制SR的钙泵活性，因此了解这两种形式之间的动态平衡是很重要的。为了考察脂质环境对SR膜上单体形式和五聚体之间平衡的影响，我们研究了不同洗涤剂和磷脂对磷蛋白低聚状态的影响。在所考察的洗涤剂中，3-[(3-cholamidopropyl)dimethylammonio]-1-propanesulfonate(CHAPS)稳定了五聚体形式，而辛基葡萄糖苷是有效的解离单体的诱导剂。基于这两种洗涤剂的这些性质，考察了在含有辛基葡萄糖苷或CHAPS的混合胶束中，不同的磷脂对磷蛋白低聚状态的影响。在所考察的8种磷脂中，磷脂酸是五聚体解离的有效诱导剂，而其他磷脂具有稳定五聚体的活性。溶血磷脂酰胆碱、溶血磷脂酰乙醇胺和磷脂酰甘油是五聚体的高效稳定剂，我们认为SR膜上的磷脂是该蛋白质单体和五聚体之间平衡的重要决定因素。结果提示，心肌SR中磷脂的代谢可能通过改变这一平衡来调节心肌的收缩能力。

Phospholamban is a reversible inhibitor of the Ca^<2+>-ATPase of the cardiac sarcoplasmic reticulum (SR) and contributes to the regulation of heart muscle contractility. Because only the monomeric form, not the pentameric form, of phospholamban inhibits the Ca^<2+>-pumping activity of the SR, it is important to understand the dynamic equilibrium between these 2 forms.To examine the effects of lipid environment on the SR membrane on the equilibrium between the monomeric form and the pentameric form of phospholmaban, we studied the effects of various detergents and phospholipids on the oligomeric state of phospholamban. Among the detergents examined, 3-[(3-cholamidopropyl)dimethylammonio]-1-propanesulfonate (CHAPS) stabilized the pentameric form whereas octylglucoside was an effective inducer of dissociation into the monomer. On the basis of these properties of the 2 detergents, the effects of various phospholipids on the oligomeric state of phospholamban with the use of mixed micelles containing octylglucoside or CHAPS were examined. Among the 8 phospholipids examined, phosphatidic acid was an effective inducer of pentamer dissociation, whereas the other phospholipids exhibited pentamer-stabilizing activity. Lysophosphatidylcholine, lysophosphatidylethanolamine, and phosphatidylglycerol were highly effective stabilizers of the pentamer.We conclude that the phospholipids in the SR membrane are important determinants of the equilibrium between the monomeric and pentameric forms of this protein. The results suggest that the metabolism of phospholipids in the cardiac SR may contribute to regulation of heart muscle contractility by shifting this equilibrium.