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.