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

受磷蛋白是心肌肌浆网（SR）Ca^<2+>-ATP酶的可逆抑制剂，有助于调节心肌收缩力。因为只有受磷蛋白的单体形式而不是五聚体形式抑制SR的Ca^2+泵活性，所以理解这两种形式之间的动态平衡是重要的。我们研究了各种去污剂和磷脂对受磷蛋白低聚状态的影响。在检查的洗涤剂中，3-[（3-胆酰胺丙基）二甲基铵基]-1-丙磺酸盐（CHAPS）稳定五聚体形式，而辛基葡糖苷是解离成单体的有效诱导剂。基于这两种洗涤剂的这些性质，研究了使用含有辛基葡糖苷或CHAPS的混合胶束时，各种磷脂对受磷蛋白低聚状态的影响。在8种磷脂中，磷脂酸是五聚体解离的有效诱导剂，而其他磷脂具有五聚体稳定活性。溶血磷脂酰胆碱，溶血磷脂酰乙醇胺，和磷脂酰甘油是非常有效的稳定剂的pentamer.We得出结论，在SR膜中的磷脂是重要的决定因素之间的平衡的单体和五聚体形式的这种蛋白质。结果表明，在心脏SR中的磷脂代谢可能有助于通过改变这种平衡来调节心肌收缩力。

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.