%0 Journal Article %1 Reut_2005_198 %A Reuter, Hannes %A Pott, Christian %A Goldhaber, Joshua I %A Henderson, Scott A %A Philipson, Kenneth D %A Schwinger, Robert H G %D 2005 %J Cardiovasc. Res. %K 15935336 Action Animals, Ca, Calcium Calcium, Cardiac, Cardiomegaly, Contraction, Disease, Electrophysiology, Energy Exchanger, Extramural, Genetic Gov't, Homozygote, Humans, Hypertrophy, Injury, Isoproterenol, Knockout, Left Metabolism, Mice, Myocardial Myocardium, Myocytes, N.I.H., Non-U.S. P.H.S., Phenotype, Potentials, Predisposition Reperfusion Research Reticulum, Sarcolemma, Sarcoplasmic Signaling, Sodium, Sodium-Calcium Support, Transgenic, U.S. Ventricular, lcium, to %N 2 %P 198--207 %R 10.1016/j.cardiores.2005.04.031 %T Na$^+$--Ca$^2+$ exchange in the regulation of cardiac excitation-contraction coupling. %U http://dx.doi.org/10.1016/j.cardiores.2005.04.031 %V 67 %X Cardiac sarcolemmal Na$^+$--Ca$^2+$ exchange is a central component of Ca$^2+$ signaling essential for Ca$^2+$ extrusion and contributing to a variable degree to the development of the systolic Ca$^2+$ transient. Reports on differential gene expression of Na$^+$--Ca$^2+$ exchange in cardiac disease and the regulation of its thermodynamic equilibrium depending on intracellular gradients of ion concentrations between subcellular compartments have recently put a new complexion on Na$^+$--Ca$^2+$ exchange and its implications for excitation-contraction (E-C) coupling. Heart failure models and genetic approaches to regulate expression of the Na$^+$--Ca$^2+$ exchanger have improved our knowledge of exchanger function. Modest overexpression of the Na$^+$--Ca$^2+$ exchanger in heterozygous transgenic mice had minimal effects on E-C coupling and cardiac function. However, higher levels of Na$^+$--Ca$^2+$ exchange expression in homozygotes led to pathological hypertrophy and failure with an increased interaction between the L-type Ca$^2+$ current and Na$^+$--Ca$^2+$ exchange and reduced E-C coupling gain. These results suggested that the Na$^+$--Ca$^2+$ exchanger is capable of modulating sarcoplasmic Ca$^2+$ handling and at high expression levels may interact with the gating kinetics of the L-type Ca$^2+$ current by means of regulating subsarcolemmal Ca$^2+$ levels. Despite being a central component in the regulation of cardiac E-C coupling, a newly generated mouse model with cardiac-specific conditional knock-out of the Na$^+$--Ca$^2+$ exchanger is viable with unchanged Ca$^2+$ dynamics in adult ventricular myocytes. Cardiac myocytes adapt well to knock-out of the exchanger, apparently by reducing transsarcolemmal fluxes of Ca$^2+$ and increasing E-C coupling gain possibly mediated by changes in submembrane Ca$^2+$ levels. For E-C coupling in the murine model, which relies primarily on sarcoplasmic Ca$^2+$ regulation, this led to the suggestion that the role of Na$^+$--Ca$^2+$ exchange should be thought of as a Ca$^2+$ buffering function and not as a major Ca$^2+$ transporter in competition with the sarcoplasmic reticulum.

@article{Reut_2005_198, abstract = {Cardiac sarcolemmal {N}a$^{+}$--{C}a$^{2+}$ exchange is a central component of {C}a$^{2+}$ signaling essential for {C}a$^{2+}$ extrusion and contributing to a variable degree to the development of the systolic {C}a$^{2+}$ transient. Reports on differential gene expression of {N}a$^{+}$--{C}a$^{2+}$ exchange in cardiac disease and the regulation of its thermodynamic equilibrium depending on intracellular gradients of ion concentrations between subcellular compartments have recently put a new complexion on {N}a$^{+}$--{C}a$^{2+}$ exchange and its implications for excitation-contraction (E-C) coupling. Heart failure models and genetic approaches to regulate expression of the {N}a$^{+}$--{C}a$^{2+}$ exchanger have improved our knowledge of exchanger function. Modest overexpression of the {N}a$^{+}$--{C}a$^{2+}$ exchanger in heterozygous transgenic mice had minimal effects on E-C coupling and cardiac function. However, higher levels of {N}a$^{+}$--{C}a$^{2+}$ exchange expression in homozygotes led to pathological hypertrophy and failure with an increased interaction between the L-type {C}a$^{2+}$ current and {N}a$^{+}$--{C}a$^{2+}$ exchange and reduced E-C coupling gain. These results suggested that the {N}a$^{+}$--{C}a$^{2+}$ exchanger is capable of modulating sarcoplasmic {C}a$^{2+}$ handling and at high expression levels may interact with the gating kinetics of the L-type {C}a$^{2+}$ current by means of regulating subsarcolemmal {C}a$^{2+}$ levels. Despite being a central component in the regulation of cardiac E-C coupling, a newly generated mouse model with cardiac-specific conditional knock-out of the {N}a$^{+}$--{C}a$^{2+}$ exchanger is viable with unchanged {C}a$^{2+}$ dynamics in adult ventricular myocytes. Cardiac myocytes adapt well to knock-out of the exchanger, apparently by reducing transsarcolemmal fluxes of {C}a$^{2+}$ and increasing E-C coupling gain possibly mediated by changes in submembrane {C}a$^{2+}$ levels. For E-C coupling in the murine model, which relies primarily on sarcoplasmic {C}a$^{2+}$ regulation, this led to the suggestion that the role of {N}a$^{+}$--{C}a$^{2+}$ exchange should be thought of as a {C}a$^{2+}$ buffering function and not as a major {C}a$^{2+}$ transporter in competition with the sarcoplasmic reticulum.}, added-at = {2009-06-03T11:20:58.000+0200}, author = {Reuter, Hannes and Pott, Christian and Goldhaber, Joshua I and Henderson, Scott A and Philipson, Kenneth D and Schwinger, Robert H G}, biburl = {https://www.bibsonomy.org/bibtex/294b78f30bd1e5f07859c2ab752ba1b2a/hake}, description = {The whole bibliography file I use.}, doi = {10.1016/j.cardiores.2005.04.031}, file = {Reut_2005_198.pdf:Reut_2005_198.pdf:PDF}, interhash = {a9615b4b4ce527b28daabc6157d31371}, intrahash = {94b78f30bd1e5f07859c2ab752ba1b2a}, journal = {Cardiovasc. Res.}, keywords = {15935336 Action Animals, Ca, Calcium Calcium, Cardiac, Cardiomegaly, Contraction, Disease, Electrophysiology, Energy Exchanger, Extramural, Genetic Gov't, Homozygote, Humans, Hypertrophy, Injury, Isoproterenol, Knockout, Left Metabolism, Mice, Myocardial Myocardium, Myocytes, N.I.H., Non-U.S. P.H.S., Phenotype, Potentials, Predisposition Reperfusion Research Reticulum, Sarcolemma, Sarcoplasmic Signaling, Sodium, Sodium-Calcium Support, Transgenic, U.S. Ventricular, lcium, to}, month = Aug, number = 2, pages = {198--207}, pii = {S0008-6363(05)00221-X}, pmid = {15935336}, timestamp = {2009-06-03T11:21:26.000+0200}, title = {{N}a$^{+}$--{C}a$^{2+}$ exchange in the regulation of cardiac excitation-contraction coupling.}, url = {http://dx.doi.org/10.1016/j.cardiores.2005.04.031}, volume = 67, year = 2005 }