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Adv Exp Med Biol. 2013;961:49-54. doi: 10.1007/978-1-4614-4756-6_5.

NCX1: mechanism of transport.

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Department of Physiology, David Geffen School of Medicine, UCLA, Los Angeles, CA 90095-1760, USA.


The plasma membrane Na(+)/Ca(2+) exchanger (NCX) plays a critical role in the maintenance of Ca(2+) homeostasis in a variety of tissues. NCX accomplishes this task by either lowering or increasing the intracellular Ca(2+) concentration, a process which depends on electrochemical gradients. During each cycle, three Na(+) are transported in the opposite direction to one Ca(2+), 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 Ca(2+) transport, Ser(110), 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 Ca(2+) translocations. Using cysteine susceptibility analysis, we demonstrated that Ser(110) is exposed to the cytoplasm when the exchanger is in the inward state configuration.

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