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Physiological Reviews, Vol. 79, No. 3, July 1999, pp. 763-854
Copyright ©1999 by the American Physiological Society
Departments of Physiology and Medicine and the Center for Vascular Biology and Hypertension, University of Maryland School of Medicine, and Department of Molecular Biology and Biophysics, The Medical Biotechnology Center of the Maryland Biotechnology Institute, Baltimore, Maryland
Blaustein, Mordecai P. and
W.
Jonathan Lederer.
Sodium/Calcium Exchange: Its Physiological Implications. Physiol. Rev. 79: 763-854, 1999.
The Na+/Ca2+
exchanger, an ion transport protein, is expressed in the plasma
membrane (PM) of virtually all animal cells. It extrudes
Ca2+ in parallel with the PM ATP-driven
Ca2+ pump. As a reversible transporter, it also mediates
Ca2+ entry in parallel with various ion channels. The
energy for net Ca2+ transport by the
Na+/Ca2+ exchanger and its direction depend on
the Na+, Ca2+, and K+ gradients
across the PM, the membrane potential, and the transport stoichiometry.
In most cells, three Na+ are exchanged for one
Ca2+. In vertebrate photoreceptors, some neurons, and
certain other cells, K+ is transported in the same
direction as Ca2+, with a coupling ratio of four
Na+ to one Ca2+ plus one K+. The
exchanger kinetics are affected by nontransported Ca2+,
Na+, protons, ATP, and diverse other modulators. Five genes
that code for the exchangers have been identified in mammals: three in
the Na+/Ca2+ exchanger family (NCX1,
NCX2, and NCX3) and two in the
Na+/Ca2+ plus K+ family
(NCKX1 and NCKX2). Genes homologous to
NCX1 have been identified in frog, squid, lobster, and
Drosophila. In mammals, alternatively spliced variants of
NCX1 have been identified; dominant expression of these
variants is cell type specific, which suggests that the variations are
involved in targeting and/or functional differences. In cardiac
myocytes, and probably other cell types, the exchanger serves a
housekeeping role by maintaining a low intracellular Ca2+
concentration; its possible role in cardiac excitation-contraction coupling is controversial. Cellular increases in Na+
concentration lead to increases in Ca2+ concentration
mediated by the Na+/Ca2+ exchanger; this is
important in the therapeutic action of cardiotonic steroids like
digitalis. Similarly, alterations of Na+ and
Ca2+ apparently modulate basolateral K+
conductance in some epithelia, signaling in some special sense organs
(e.g., photoreceptors and olfactory receptors) and
Ca2+-dependent secretion in neurons and in many secretory
cells. The juxtaposition of PM and sarco(endo)plasmic reticulum
membranes may permit the PM Na+/Ca2+ exchanger
to regulate sarco(endo)plasmic reticulum Ca2+ stores and
influence cellular Ca2+ signaling.
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 C. Jimenez-Gonzalez, F. Michelangeli, C.V. Harper, C.L.R. Barratt, and S.J. Publicover Calcium signalling in human spermatozoa: a specialized 'toolkit' of channels, transporters and stores Hum. Reprod. Update, May 1, 2006; 12(3): 253 - 267. [Abstract] [Full Text] [PDF]
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J. Inserte, D. Garcia-Dorado, V. Hernando, I. Barba, and J. Soler-Soler Ischemic preconditioning prevents calpain-mediated impairment of Na+/K+-ATPase activity during early reperfusion Cardiovasc Res, May 1, 2006; 70(2): 364 - 373. [Abstract] [Full Text] [PDF]
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 S. Geibel, N. Flores-Herr, T. Licher, and H. Vollert Establishment of Cell-Free Electrophysiology for Ion Transporters: Application for Pharmacological Profiling J Biomol Screen, April 1, 2006; 11(3): 262 - 268. [Abstract] [PDF]
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K. W. Dilly, C. F. Rossow, V. S. Votaw, J. S. Meabon, J. L. Cabarrus, and L. F. Santana Mechanisms underlying variations in excitation-contraction coupling across the mouse left ventricular free wall J. Physiol., April 1, 2006; 572(1): 227 - 241. [Abstract] [Full Text] [PDF]
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X.-F. Li, L. Kiedrowski, F. Tremblay, F. R. Fernandez, M. Perizzolo, R. J. Winkfein, R. W. Turner, J. S. Bains, D. E. Rancourt, and J. Lytton Importance of K+-dependent Na+/Ca2+-exchanger 2, NCKX2, in Motor Learning and Memory J. Biol. Chem., March 10, 2006; 281(10): 6273 - 6282. [Abstract] [Full Text] [PDF]
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T. Iwamoto Vascular Na+/Ca2+ exchanger: implications for the pathogenesis and therapy of salt-dependent hypertension Am J Physiol Regulatory Integrative Comp Physiol, March 1, 2006; 290(3): R536 - R545. [Abstract] [Full Text] [PDF]
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Z.-Q. Wu, M. Li, J. Chen, Z.-Q. Chi, and J.-G. Liu Involvement of cAMP/cAMP-Dependent Protein Kinase Signaling Pathway in Regulation of Na+,K+-ATPase upon Activation of Opioid Receptors by Morphine Mol. Pharmacol., March 1, 2006; 69(3): 866 - 876. [Abstract] [Full Text] [PDF]
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M. Condrescu and J. P. Reeves Actin-dependent regulation of the cardiac Na+/Ca2+ exchanger Am J Physiol Cell Physiol, March 1, 2006; 290(3): C691 - C701. [Abstract] [Full Text] [PDF]
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J. M. Dai, K.-H. Kuo, J. M. Leo, C. van Breemen, and C.-H. Lee Mechanism of ACh-induced asynchronous calcium waves and tonic contraction in porcine tracheal muscle bundle Am J Physiol Lung Cell Mol Physiol, March 1, 2006; 290(3): L459 - L469. [Abstract] [Full Text] [PDF]
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S.-i. Sekizawa and A. C. Bonham Group I Metabotropic Glutamate Receptors on Second-Order Baroreceptor Neurons Are Tonically Activated and Induce a Na+-Ca2+ Exchange Current J Neurophysiol, February 1, 2006; 95(2): 882 - 892. [Abstract] [Full Text] [PDF]
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M. Yamasaki, K. Hashimoto, and M. Kano Miniature Synaptic Events Elicited by Presynaptic Ca2+ Rise Are Selectively Suppressed by Cannabinoid Receptor Activation in Cerebellar Purkinje Cells J. Neurosci., January 4, 2006; 26(1): 86 - 95. [Abstract] [Full Text] [PDF]
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 R. Dipolo and L. Beauge Sodium/Calcium Exchanger: Influence of Metabolic Regulation on Ion Carrier Interactions Physiol Rev, January 1, 2006; 86(1): 155 - 203. [Abstract] [Full Text] [PDF]
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N. McHale, M. Hollywood, G. Sergeant, and K. Thornbury Origin of spontaneous rhythmicity in smooth muscle J. Physiol., January 1, 2006; 570(1): 23 - 28. [Abstract] [Full Text] [PDF]
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 D. Burdakov, S. M Luckman, and A. Verkhratsky Glucose-sensing neurons of the hypothalamus Phil Trans R Soc B, December 29, 2005; 360(1464): 2227 - 2235. [Abstract] [Full Text] [PDF]
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J.-C. Platel, S. Boisseau, A. Dupuis, J. Brocard, A. Poupard, M. Savasta, M. Villaz, and M. Albrieux Na+ channel-mediated Ca2+ entry leads to glutamate secretion in mouse neocortical preplate PNAS, December 27, 2005; 102(52): 19174 - 19179. [Abstract] [Full Text] [PDF]
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A. D. Langenbacher, Y. Dong, X. Shu, J. Choi, D. A. Nicoll, J. I. Goldhaber, K. D. Philipson, and J.-N. Chen Mutation in sodium-calcium exchanger 1 (NCX1) causes cardiac fibrillation in zebrafish PNAS, December 6, 2005; 102(49): 17699 - 17704. [Abstract] [Full Text] [PDF]
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J. Zhang, M. Y. Lee, M. Cavalli, L. Chen, R. Berra-Romani, C. W. Balke, G. Bianchi, P. Ferrari, J. M. Hamlyn, T. Iwamoto, et al. Sodium pump {alpha}2 subunits control myogenic tone and blood pressure in mice J. Physiol., November 15, 2005; 569(1): 243 - 256. [Abstract] [Full Text] [PDF]
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J. A. Wasserstrom and G. L. Aistrup Digitalis: new actions for an old drug Am J Physiol Heart Circ Physiol, November 1, 2005; 289(5): H1781 - H1793. [Abstract] [Full Text] [PDF]
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K. R. Sipido and D. Eisner Something old, something new: Changing views on the cellular mechanisms of heart failure Cardiovasc Res, November 1, 2005; 68(2): 167 - 174. [Full Text] [PDF]
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A. Omelchenko, R. Bouchard, S. Shurraw, M. Trac, M. Hnatowich, and L. V. Hryshko Frequency-dependent regulation of cardiac Na+/Ca2+ exchanger Am J Physiol Heart Circ Physiol, October 1, 2005; 289(4): H1594 - H1603. [Abstract] [Full Text] [PDF]
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J. Inserte, D. Garcia-Dorado, V. Hernando, and J. Soler-Soler Calpain-Mediated Impairment of Na+/K+-ATPase Activity During Early Reperfusion Contributes to Cell Death After Myocardial Ischemia Circ. Res., September 2, 2005; 97(5): 465 - 473. [Abstract] [Full Text] [PDF]
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Z. Zhang, C. Cao, W. Lee-Kwon, and T. L. Pallone Descending vasa recta pericytes express voltage operated Na+ conductance in the rat J. Physiol., September 1, 2005; 567(2): 445 - 457. [Abstract] [Full Text] [PDF]
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S. Lambert and J. Oberwinkler Characterization of a proton-activated, outwardly rectifying anion channel J. Physiol., August 15, 2005; 567(1): 191 - 213. [Abstract] [Full Text] [PDF]
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C. R. Marshall, T.-C. Pan, H. D. Le, A. Omelchenko, P. P. Hwang, L. V. Hryshko, and G. F. Tibbits cDNA Cloning and Expression of the Cardiac Na+/Ca2+ Exchanger from Mozambique Tilapia (Oreochromis mossambicus) Reveal a Teleost Membrane Transporter with Mammalian Temperature Dependence J. Biol. Chem., August 12, 2005; 280(32): 28903 - 28911. [Abstract] [Full Text] [PDF]
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H. Reuter, C. Pott, J. I. Goldhaber, S. A. Henderson, K. D. Philipson, and R. H.G. Schwinger Na+-Ca2+exchange in the regulation of cardiac excitation-contraction coupling Cardiovasc Res, August 1, 2005; 67(2): 198 - 207. [Abstract] [Full Text] [PDF]
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L. Weigand, J. Foxson, J. Wang, L. A. Shimoda, and J. T. Sylvester Inhibition of hypoxic pulmonary vasoconstriction by antagonists of store-operated Ca2+ and nonselective cation channels Am J Physiol Lung Cell Mol Physiol, July 1, 2005; 289(1): L5 - L13. [Abstract] [Full Text] [PDF]
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L. Beauge and R. DiPolo SEA-0400, a potent inhibitor of the Na+/Ca2+ exchanger, as a tool to study exchanger ionic and metabolic regulation Am J Physiol Cell Physiol, June 1, 2005; 288(6): C1374 - C1380. [Abstract] [Full Text] [PDF]
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J. Wang, L. A. Shimoda, L. Weigand, W. Wang, D. Sun, and J. T. Sylvester Acute hypoxia increases intracellular [Ca2+] in pulmonary arterial smooth muscle by enhancing capacitative Ca2+ entry Am J Physiol Lung Cell Mol Physiol, June 1, 2005; 288(6): L1059 - L1069. [Abstract] [Full Text] [PDF]
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D. von Lewinski, S. Bruns, S. Walther, H. Kogler, and B. Pieske Insulin Causes [Ca2+]i-Dependent and [Ca2+]i-Independent Positive Inotropic Effects in Failing Human Myocardium Circulation, May 24, 2005; 111(20): 2588 - 2595. [Abstract] [Full Text] [PDF]
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V. Haufe, J. A. Camacho, R. Dumaine, B. Gunther, C. Bollensdorff, G. S. von Banchet, K. Benndorf, and T. Zimmer Expression pattern of neuronal and skeletal muscle voltage-gated Na+ channels in the developing mouse heart J. Physiol., May 1, 2005; 564(3): 683 - 696. [Abstract] [Full Text] [PDF]
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