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Unless otherwise stated all data on this page refer to the human proteins. Gene information is provided for human (Hs), mouse (Mm) and rat (Rn).
The sodium/calcium exchangers (NCX) use the extracellular sodium concentration to facilitate the extrusion of calcium out of the cell. Alongside the plasma membrane Ca2+-ATPase (PMCA) and sarcoplasmic/endoplasmic reticulum Ca2+-ATPase (SERCA), as well as the sodium/potassium/calcium exchangers (NKCX, SLC24 family), NCX allow recovery of intracellular calcium back to basal levels after cellular stimulation. When intracellular sodium ion levels rise, for example, following depolarisation, these transporters can operate in the reverse direction to allow calcium influx and sodium efflux, as an electrogenic mechanism. Structural modelling suggests the presence of 9 TM segments, with a large intracellular loop between the fifth and sixth TM segments.
* Key recommended reading is highlighted with an asterisk
* Annunziato L, Pignataro G, Di Renzo GF. (2004) Pharmacology of brain Na+/Ca2+ exchanger: from molecular biology to therapeutic perspectives. Pharmacol. Rev., 56 (4): 633-54. [PMID:15602012]
Gabellini N. (2004) Transcriptional regulation by cAMP and Ca2+ links the Na+/Ca2+ exchanger 3 to memory and sensory pathways. Mol. Neurobiol., 30 (1): 91-116. [PMID:15247490]
* Khananshvili D. (2014) Sodium-calcium exchangers (NCX): molecular hallmarks underlying the tissue-specific and systemic functions. Pflugers Arch., 466 (1): 43-60. [PMID:24281864]
* Lytton J. (2007) Na+/Ca2+ exchangers: three mammalian gene families control Ca2+ transport. Biochem. J., 406 (3): 365-82. [PMID:17716241]
* Quednau BD, Nicoll DA, Philipson KD. (2004) The sodium/calcium exchanger family-SLC8. Pflugers Arch., 447 (5): 543-8. [PMID:12734757]
* Watanabe Y, Koide Y, Kimura J. (2006) Topics on the Na+/Ca2+ exchanger: pharmacological characterization of Na+/Ca2+ exchanger inhibitors. J. Pharmacol. Sci., 102 (1): 7-16. [PMID:16990699]
Zhang YH, Hancox JC. (2009) Regulation of cardiac Na+-Ca2+ exchanger activity by protein kinase phosphorylation--still a paradox?. Cell Calcium, 45 (1): 1-10. [PMID:18614228]
1. Dong H, Dunn J, Lytton J. (2002) Stoichiometry of the Cardiac Na+/Ca2+ exchanger NCX1.1 measured in transfected HEK cells. Biophys. J., 82 (4): 1943-52. [PMID:11916852]
2. Iwamoto T, Kita S. (2006) YM-244769, a novel Na+/Ca2+ exchange inhibitor that preferentially inhibits NCX3, efficiently protects against hypoxia/reoxygenation-induced SH-SY5Y neuronal cell damage. Mol. Pharmacol., 70 (6): 2075-83. [PMID:16973719]
3. Jost N, Nagy N, Kohajda Z, Horváth A, Corici C, Acsai K, Biliczki P, Levijoki J, Pollesello P, Koskelainen T et al.. (2013) ORM-10103, a novel specific inhibitor of the sodium/calcium exchanger, decreases early and delayed afterdepolarization in the canine heart. Br. J. Pharmacol., [Epub ahead of print]. [PMID:23647096]
4. Secondo A, Pignataro G, Ambrosino P, Pannaccione A, Molinaro P, Boscia F, Cantile M, Cuomo O, Esposito A, Sisalli MJ et al.. (2015) Pharmacological characterization of the newly synthesized 5-amino-N-butyl-2-(4-ethoxyphenoxy)-benzamide hydrochloride (BED) as a potent NCX3 inhibitor that worsens anoxic injury in cortical neurons, organotypic hippocampal cultures, and ischemic brain. ACS Chem Neurosci, 6 (8): 1361-70. [PMID:25942323]
Database page citation:
Jules Hancox. SLC8 family of sodium/calcium exchangers. Accessed on 26/04/2017. IUPHAR/BPS Guide to PHARMACOLOGY, http://www.guidetopharmacology.org/GRAC/FamilyDisplayForward?familyId=180.
Concise Guide to PHARMACOLOGY citation:
Alexander SPH, Kelly E, Marrion N, Peters JA, Benson HE, Faccenda E, Pawson AJ, Sharman JL, Southan C, Davies JA and CGTP Collaborators (2015) The Concise Guide to PHARMACOLOGY 2015/16: Transporters. Br J Pharmacol. 172: 6110-6202.