Encyclopedia of Molecular Pharmacology

Living Edition
| Editors: Stefan Offermanns, Walter Rosenthal

Na+/Ca2+ Exchangers

  • Lucio AnnunziatoEmail author
  • Giuseppe Pignataro
  • Pasquale Molinaro
Living reference work entry
DOI: https://doi.org/10.1007/978-3-030-21573-6_192-1



The plasma membrane Na+/Ca2+ exchanger is a high-capacity and low-affinity ionic transporter that exchanges three Na+ ions for one Ca2+ ion. When intracellular Ca2+ concentrations ([Ca2+]i) rise and the cells require the return to resting levels, this exchanger couples the uphill extrusion of Ca2+ ions to the influx of Na+ ions into the cells down their electrochemical gradient. This mode of operation, defined as forward mode, or Ca2+ efflux mechanism, keeps the 104-fold difference in [Ca2+]i across the cell membrane. Under other physiological or pathophysiological conditions when the intracellular Na+ concentrations ([Na+]i) rise, or membrane depolarization occurs and reduces the transmembrane Na+ electrochemical gradient, the Na+/Ca2+ exchanger mediates the extrusion of Na+ and the influx of Ca2+ ions. This last mode of operation is defined as reverse mode or Ca2+influx...

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CBD1 and CBD2

Calcium binding domain 1 and 2 of the f loop

f loop

Intracellular domain between transmembrane segments 5 and 6 of the sodium calcium exchanger

Forward or Ca2+ efflux mode

Mode of operation of NCX extruding calcium and intruding sodium ions

Na+-dependent Ca2+ uptake

Calcium uptake elicited by reduced concentrations of extracellular sodium


Phosphatidylinositol 4,5 bisphosphate

Reverse or Ca2+ influx mode

Mode of operation of NCX extruding sodium and intruding calcium ions


20 amino acid region of the f loop of the sodium calcium exchanger


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© Springer-Verlag Berlin Heidelberg New York 2020

Authors and Affiliations

  • Lucio Annunziato
    • 1
    Email author
  • Giuseppe Pignataro
    • 1
  • Pasquale Molinaro
    • 1
  1. 1.Division of Pharmacology, Department of Neuroscience, School of Medicine“Federico II” University of NaplesNaplesItaly