Enyedi A, Minami J, Caride A J, Penniston J T
Department of Biochemistry and Molecular Biology, Mayo Clinic, Rochester, MN 55905.
Biochem J. 1988 May 15;252(1):215-20. doi: 10.1042/bj2520215.
A plasma membrane-enriched fraction from rat myometrium shows ATP-Mg2+-dependent active calcium uptake which is independent of the presence of oxalate and is abolished by the Ca2+ ionophore A23187. Ca2+ loaded into vesicles via the ATP-dependent Ca2+ uptake was released by extravesicular Na+. This showed that the Na+/Ca2+ exchange and the Ca2+ uptake were both occurring in plasma membrane vesicles. In a medium containing KCl, vanadate readily inhibited the Ca2+ uptake (K1/2 5 microM); when sucrose replaced KCl, 400 microM-vanadate was required for half inhibition. Only a slight stimulation of the calcium pump by calmodulin was observed in untreated membrane vesicles. Extraction of endogenous calmodulin from the membranes by EGTA decreased the activity and Ca2+ affinity of the calcium pump; both activity and affinity were fully restored by adding back calmodulin or by limited proteolysis. A monoclonal antibody (JA3) directed against the human erythrocyte Ca2+ pump reacted with the 140 kDa Ca2+-pump protein of the myometrial plasma membrane. The Ca2+-ATPase activity of these membranes is not specific for ATP, and is not inhibited by mercurial agents, whereas Ca2+ uptake has the opposite properties. Ca2+-ATPase activity is also over 100 times that of calcium transport; it appears that the ATPase responsible for transport is largely masked by the presence of another Ca2+-ATPase of unknown function. Measurements of total Ca2+-ATPase activity are, therefore, probably not directly relevant to the question of intracellular Ca2+ control.
大鼠子宫肌层富含质膜的组分显示出ATP-Mg²⁺依赖性的活性钙摄取,该摄取不依赖于草酸盐的存在,且被Ca²⁺离子载体A23187所消除。通过ATP依赖性钙摄取加载到囊泡中的Ca²⁺被囊泡外的Na⁺释放。这表明Na⁺/Ca²⁺交换和Ca²⁺摄取都发生在质膜囊泡中。在含有KCl的培养基中,钒酸盐很容易抑制Ca²⁺摄取(半数抑制浓度K1/2为5 microM);当蔗糖替代KCl时,半数抑制需要400 microM钒酸盐。在未处理的膜囊泡中仅观察到钙调蛋白对钙泵有轻微刺激作用。用EGTA从膜中提取内源性钙调蛋白会降低钙泵的活性和Ca²⁺亲和力;通过重新添加钙调蛋白或有限的蛋白酶解可使活性和亲和力完全恢复。一种针对人红细胞Ca²⁺泵的单克隆抗体(JA3)与子宫肌层质膜的140 kDa Ca²⁺泵蛋白发生反应。这些膜的Ca²⁺-ATP酶活性对ATP不具有特异性,且不受汞剂抑制,而Ca²⁺摄取则具有相反的特性。Ca²⁺-ATP酶活性也比钙转运活性高100倍以上;看来负责转运的ATP酶在很大程度上被另一种功能未知的Ca²⁺-ATP酶所掩盖。因此,总Ca²⁺-ATP酶活性的测量可能与细胞内Ca²⁺控制问题没有直接关系。