NCX1: Mechanism of transport

Abstract

The plasma membrane Na+/Ca2+ exchanger (NCX) plays a critical role in the maintenance of Ca2+ homeostasis in a variety of tissues. NCX accomplishes this task by either lowering or increasing the intracellular Ca2+ concentration, a process which depends on electrochemical gradients. During each cycle, three Na+ are transported in the opposite direction to one Ca2+, resulting in an electrogenic transport that can be measured as an ionic current. The residues involved in ion translocation are unknown. A residue thought to be important for Na+ and/or Ca2+ transport, Ser110, was replaced with a cysteine, and the properties of the resulting exchanger mutant were analyzed using the giant patch technique. Data indicate that this residue, located in transmembrane segment 2 (part of the α-1 repeat), is important for both Na+ and Ca2+ translocations. Using cysteine susceptibility analysis, we demonstrated that Ser110 is exposed to the cytoplasm when the exchanger is in the inward state configuration. © Springer Science+Business Media New York 2013.