Herchuelz André, Kamagate Adama, Ximenes Helena, Van Eylen Françoise
Laboratory of Pharmacology, Brussels University School of Medicine, B-1070, Brussels, Belgium.
Ann N Y Acad Sci. 2007 Mar;1099:456-67. doi: 10.1196/annals.1387.048.
Recent progresses concerning the Na/Ca exchanger (NCX) and the plasma membrane Ca2+-ATPase (PMCA) in the pancreatic beta cell are reviewed. The rat beta cell expresses two splice variants of NCX1 and six splice variants of the 4 PMCA isoforms. At the protein level, the most abundant forms are PMCA2 and PMCA3, providing the first evidence for the presence of these two isoforms in a non-neuronal tissue. Overexpression of NCX1 in an insulinoma cell line altered the initial rise in cytosolic-free Ca2+ concentration ([Ca2+]i) induced by membrane depolarization and the return of the [Ca2+]i to the baseline value on membrane repolarization, indicating that NCX contributes to both Ca2+ inflow and outflow in the beta cell. In contrast, overexpression of the PMCA markedly reduced the global rise in Ca2+ induced by membrane depolarization, indicating that the PMCA has a capacity higher than expected to extrude Ca2+. Glucose, the main physiological stimulus of insulin release from the beta cell, has opposite effect on NCX and PMCA transcription, expression and activity, inducing an increase in the case of NCX and a decrease in the case of the PMCA. This indicates that when exposed to glucose, the beta cell switches from a low-efficiency Ca2+ extruding mechanism, the PMCA, to a high-capacity system, the NCX, in order to better face the increase in Ca2+ inflow induced by the sugar. To our knowledge, this is the first demonstration of a reciprocal change in PMCA and NCX1 expression and activity in response to a given stimulus in any tissue.
本文综述了胰腺β细胞中钠钙交换体（NCX）和质膜钙ATP酶（PMCA）的最新研究进展。大鼠β细胞表达NCX1的两种剪接变体和4种PMCA亚型的6种剪接变体。在蛋白质水平上，最丰富的形式是PMCA2和PMCA3，这首次证明了这两种亚型在非神经组织中的存在。在胰岛素瘤细胞系中过表达NCX1改变了膜去极化诱导的胞质游离钙浓度（[Ca2+]i）的初始升高以及膜复极化时[Ca2+]i恢复到基线值的情况，表明NCX参与了β细胞中钙的流入和流出。相反，PMCA的过表达显著降低了膜去极化诱导的钙的整体升高，表明PMCA具有高于预期的钙外排能力。葡萄糖是β细胞释放胰岛素的主要生理刺激物，对NCX和PMCA的转录、表达和活性有相反的影响，使NCX增加而使PMCA减少。这表明当暴露于葡萄糖时，β细胞从低效的钙外排机制PMCA切换到高容量系统NCX，以便更好地应对糖诱导的钙流入增加。据我们所知，这是首次证明在任何组织中，PMCA和NCX1的表达和活性会因给定刺激而发生相互变化。
