Role of Na/Ca exchange and the plasma membrane Ca 2+ ‐ATPase in cell function

Abstract

The Fifth International Conference on Na/Ca Exchange took place between 23 and 27 August 2006 in Brussels, Belgium, and was organized by A. Herchuelz. Image taken from the meeting poster showing hypothetical models for the Na/Ca exchanger (left) and the plasma membrane Ca2+‐ATPase (right), courtesy of M. Hilge. ![][1] Cytosolic Ca2+ regulates several cellular processes and its concentration is, in turn, finely regulated by various channels, pumps and exchangers. The Na/Ca exchanger (NCX) and the plasma membrane Ca2+‐ATPase (PMCA) pump are two concurrent mechanisms for Ca2+ extrusion from the cell (Carafoli, 1994; Blaustein & Lederer, 1999; Philipson & Nicoll, 2000; Strehler & Treiman, 2004; Prasad et al , 2004). PMCA and NCX were cloned 17 and 19 years ago, respectively; four mammalian isoforms have been identified for the former (PMCA1–4) and three have been identified for the latter (NCX1–3; Carafoli, 1994; Philipson & Nicoll, 2000). Na/Ca exchange (NCX) is a unique mechanism that allows Ca2+ extrusion from the cell against its gradient without energy consumption. Indeed, it is the entry of Na+ along its electrochemical gradient that provides the energy for Ca2+ extrusion. In addition, because NCX is electrogenic and voltage sensitive, it can reverse during cellular activation and contribute to Ca2+ entry into the cell (Blaustein & Lederer, 1999). Recently, the crucial role of NCX in cellular Ca2+ homeostasis has been definitively shown by the generation of mice with functional destruction of one Ncx gene. Homozygous Ncx1 ‐deficient mice are not viable, and die between embryonic days 9 and 10, owing to the lack of development of the cardiovascular system (Wakimoto et al , 2000); therefore, NCX is essential for life. PMCA belongs to the P‐type family of transport ATPases, which form a phosphorylated intermediate … [1]: /embed/graphic-1.gif