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肌浆网Ca²⁺-ATP酶(SERCA)的质子泵功能能否增强受磷蛋白和肌浆脂质蛋白的调节作用?

Can proton pumping by SERCA enhance the regulatory role of phospholamban and sarcolipin?

作者信息

Becucci Lucia, Foresti Maria Luisa, Schwan Adrian, Guidelli Rolando

机构信息

Department of Chemistry, University of Padova, Via Marzolo 1, 35131, Padova, Italy.

出版信息

Biochim Biophys Acta. 2013 Nov;1828(11):2682-90. doi: 10.1016/j.bbamem.2013.07.012. Epub 2013 Jul 18.

DOI:10.1016/j.bbamem.2013.07.012
PMID:23872124
Abstract

The effect of the incorporation of phosphorylated phospholamban (pPLN) and sarcolipin (SLN) in mercury-supported self-assembled lipid monolayers and in lipid bilayers tethered to mercury via a hydrophilic spacer was investigated by voltammetric techniques and electrochemical impedance spectroscopy. It was shown that pPLN and SLN do not permeabilize lipid bilayers toward ions at physiological pH. However, they exert a permeabilizing action toward inorganic monovalent cations such as K(+) and Tl(+), but not toward divalent cations such as Ca(2+) and Cd(2+), following a small decrease in pH. This behavior can be associated with their regulatory action on the Ca-ATPase of the sarcoplasmic reticulum (SERCA). SERCA pumps two Ca(2+) ions from the cytosol to the lumen of the sarcoplasmic reticulum (SR) and two protons in the opposite direction, causing a transient decrease of pH in the immediate vicinity of its cytoplasmic domain. This decrease is expected to activate the liberated pPLN molecules and SLN to make the SR membrane leakier toward K(+) and Na(+) and the SLN ion channel to translocate small inorganic anions, such as Cl(-). The effect of pPLN and SLN, which becomes synergic when they are both present in the SR membrane, is expected to favor a rapid equilibration of ions on both sides of the membrane.

摘要

通过伏安法技术和电化学阻抗谱研究了磷酸化受磷蛋白(pPLN)和肌浆蛋白(SLN)掺入汞支撑的自组装脂质单层以及通过亲水性间隔物与汞相连的脂质双层中的效果。结果表明,在生理pH值下,pPLN和SLN不会使脂质双层对离子具有通透性。然而,在pH值略有下降后,它们对诸如K(+)和Tl(+)等无机单价阳离子具有通透作用,但对诸如Ca(2+)和Cd(2+)等二价阳离子则没有通透作用。这种行为可能与其对肌浆网(SERCA)的钙ATP酶的调节作用有关。SERCA将两个Ca(2+)离子从细胞质泵入肌浆网(SR)腔,并将两个质子泵向相反方向,导致其细胞质结构域附近的pH值暂时下降。预计这种下降会激活释放的pPLN分子和SLN,使SR膜对K(+)和Na(+)的通透性增加,并且使SLN离子通道转运诸如Cl(-)等小的无机阴离子。当pPLN和SLN同时存在于SR膜中时,它们的作用具有协同性,预计这将有利于膜两侧离子的快速平衡。

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