%0 Journal Article %1 Blau_1999_763 %A Blaustein, M. P. %A Lederer, W. J. %D 1999 %J Physiol. Rev. %K 10390518 Acid Amino Animals, Base Data, Exchanger, Gov't, Humans, Kinetics, Molecular P.H.S., Relationship, Research Sequence Sequence, Sodium-Calcium Structure-Activity Support, U.S. %N 3 %P 763--854 %T Sodium/calcium exchange: its physiological implications. %U http://physrev.physiology.org/cgi/content/full/79/3/763 %V 79 %X The Na$^+$/Ca$^2+$ exchanger, an ion transport protein, is expressed in the plasma membrane (PM) of virtually all animal cells. It extrudes Ca$^2+$ in parallel with the PM ATP-driven Ca$^2+$ pump. As a reversible transporter, it also mediates Ca$^2+$ entry in parallel with various ion channels. The energy for net Ca$^2+$ transport by the Na$^+$/Ca$^2+$ exchanger and its direction depend on the Na$^+$, Ca$^2+$, and K$^+$ gradients across the PM, the membrane potential, and the transport stoichiometry. In most cells, three Na$^+$ are exchanged for one Ca$^2+$. In vertebrate photoreceptors, some neurons, and certain other cells, K$^+$ is transported in the same direction as Ca$^2+$, with a coupling ratio of four Na$^+$ to one Ca$^2+$ plus one K$^+$. The exchanger kinetics are affected by nontransported Ca$^2+$, Na$^+$, protons, ATP, and diverse other modulators. Five genes that code for the exchangers have been identified in mammals: three in the Na$^+$/Ca$^2+$ exchanger family (NCX1, NCX2, and NCX3) and two in the Na$^+$/Ca$^2+$ 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 Ca$^2+$ concentration; its possible role in cardiac excitation-contraction coupling is controversial. Cellular increases in Na$^+$ concentration lead to increases in Ca$^2+$ concentration mediated by the Na$^+$/Ca$^2+$ exchanger; this is important in the therapeutic action of cardiotonic steroids like digitalis. Similarly, alterations of Na$^+$ and Ca$^2+$ apparently modulate basolateral K$^+$ conductance in some epithelia, signaling in some special sense organs (e.g., photoreceptors and olfactory receptors) and Ca$^2+$-dependent secretion in neurons and in many secretory cells. The juxtaposition of PM and sarco(endo)plasmic reticulum membranes may permit the PM Na$^+$/Ca$^2+$ exchanger to regulate sarco(endo)plasmic reticulum Ca$^2+$ stores and influence cellular Ca$^2+$ signaling.

@article{Blau_1999_763, abstract = {The {N}a$^{+}$/{C}a$^{2+}$ exchanger, an ion transport protein, is expressed in the plasma membrane ({PM}) of virtually all animal cells. It extrudes {C}a$^{2+}$ in parallel with the {PM} ATP-driven {C}a$^{2+}$ pump. As a reversible transporter, it also mediates {C}a$^{2+}$ entry in parallel with various ion channels. The energy for net {C}a$^{2+}$ transport by the {N}a$^{+}$/{C}a$^{2+}$ exchanger and its direction depend on the {N}a$^{+}$, {C}a$^{2+}$, and {K}$^{+}$ gradients across the {PM}, the membrane potential, and the transport stoichiometry. In most cells, three {N}a$^{+}$ are exchanged for one {C}a$^{2+}$. In vertebrate photoreceptors, some neurons, and certain other cells, {K}$^{+}$ is transported in the same direction as {C}a$^{2+}$, with a coupling ratio of four {N}a$^{+}$ to one {C}a$^{2+}$ plus one {K}$^{+}$. The exchanger kinetics are affected by nontransported {C}a$^{2+}$, {N}a$^{+}$, protons, ATP, and diverse other modulators. Five genes that code for the exchangers have been identified in mammals: three in the {N}a$^{+}$/{C}a$^{2+}$ exchanger family (NCX1, NCX2, and NCX3) and two in the {N}a$^{+}$/{C}a$^{2+}$ plus {K}$^{+}$ family ({NCKX}1 and {NCKX}2). 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 {C}a$^{2+}$ concentration; its possible role in cardiac excitation-contraction coupling is controversial. Cellular increases in {N}a$^{+}$ concentration lead to increases in {C}a$^{2+}$ concentration mediated by the {N}a$^{+}$/{C}a$^{2+}$ exchanger; this is important in the therapeutic action of cardiotonic steroids like digitalis. Similarly, alterations of {N}a$^{+}$ and {C}a$^{2+}$ apparently modulate basolateral {K}$^{+}$ conductance in some epithelia, signaling in some special sense organs (e.g., photoreceptors and olfactory receptors) and {C}a$^{2+}$-dependent secretion in neurons and in many secretory cells. The juxtaposition of {PM} and sarco(endo)plasmic reticulum membranes may permit the {PM} {N}a$^{+}$/{C}a$^{2+}$ exchanger to regulate sarco(endo)plasmic reticulum {C}a$^{2+}$ stores and influence cellular {C}a$^{2+}$ signaling.}, added-at = {2009-06-03T11:20:58.000+0200}, author = {Blaustein, M. P. and Lederer, W. J.}, biburl = {https://www.bibsonomy.org/bibtex/298f90c178bf9408416abb6803c21cbe9/hake}, description = {The whole bibliography file I use.}, file = {Blau_1999_763.pdf:Blau_1999_763.pdf:PDF}, interhash = {029e0d8de35f09fcda9c42cc67f4620e}, intrahash = {98f90c178bf9408416abb6803c21cbe9}, journal = {Physiol. Rev.}, key = 74, keywords = {10390518 Acid Amino Animals, Base Data, Exchanger, Gov't, Humans, Kinetics, Molecular P.H.S., Relationship, Research Sequence Sequence, Sodium-Calcium Structure-Activity Support, U.S.}, month = Jul, number = 3, pages = {763--854}, pmid = {10390518}, timestamp = {2009-06-03T11:21:05.000+0200}, title = {Sodium/calcium exchange: its physiological implications.}, url = {http://physrev.physiology.org/cgi/content/full/79/3/763}, volume = 79, year = 1999 }