%0 Journal Article %1 Fan_1996_5527 %A Fan, J. %A Shuba, Y. M. %A Morad, M. %D 1996 %J Proc. Natl. Acad. Sci. U. S. A. %K 8-Bromo 8643609 AMP, ATPase, Action Adenosine Adenylate Adrenergic Adrenergic, Animals, Calcium, Carrier Comparative Contraction, Cyclase, Cyclic Exchanger, Forskolin, Gov't, Heart Heart, In Isoproterenol, Kinetics, Membrane Monophosphate, Myocardial Nickel, Non-U.S. P.H.S., Patch-Clamp Potentials, Propranolol, Proteins, Rana Receptors, Research Reticulum, Sarcoplasmic Sodium-Calcium Study, Support, Techniques, Theophylline, U.S. Ventricles, Vitro, beta, beta-Agonists, beta-Antagonists, pipiens, {C}a$^{2+}$-Transporting %N 11 %P 5527-32 %T Regulation of cardiac sodium-calcium exchanger by beta-adrenergic agonists. %V 93 %X Na$^+$-Ca$^2+$ exchanger and Ca$^2+$ channel are two major sarcolemmal Ca$^2+$-transporting proteins of cardiac myocytes. Although the Ca$^2+$ channel is effectively regulated by protein kinase A-dependent phosphorylation, no enzymatic regulation of the exchanger protein has been identified as yet. Here we report that in frog ventricular myocytes, isoproterenol down-regulates the Na$^+$-Ca$^2+$ exchanger, independent of intracellular Ca$^2+$ and membrane potential, by activation of the beta-receptor/adenylate-cyclase/cAMP-dependent cascade, resulting in suppression of transmembrane Ca$^2+$ transport via the exchanger and providing for the well-documented contracture-suppressant effect of the hormone on frog heart. The beta-blocker propranolol blocks the isoproterenol effect, whereas forskolin, cAMP, and theophylline mimic it. In the frog heart where contractile Ca$^2+$ is transported primarily by the Na$^+$-Ca$^2+$ exchanger, the beta-agonists' simultaneous enhancement of Ca$^2+$ current, ICa, and suppression of Na$^+$-Ca$^2+$ exchanger current, INa-Ca would enable the myocyte to develop force rapidly at the onset of depolarization (enhancement of ICa) and to decrease Ca$^2+$ influx (suppression of INa-Ca) later in the action potential. This unique adrenergically induced shift in the Ca$^2+$ influx pathways may have evolved in response to paucity of the sarcoplasmic reticulum Ca$^2+$-ATPase/phospholamban complex and absence of significant intracellular Ca$^2+$ release pools in the frog heart.

@article{Fan_1996_5527, abstract = {{N}a$^{+}$-{C}a$^{2+}$ exchanger and {C}a$^{2+}$ channel are two major sarcolemmal {C}a$^{2+}$-transporting proteins of cardiac myocytes. Although the {C}a$^{2+}$ channel is effectively regulated by protein kinase A-dependent phosphorylation, no enzymatic regulation of the exchanger protein has been identified as yet. Here we report that in frog ventricular myocytes, isoproterenol down-regulates the {N}a$^{+}$-{C}a$^{2+}$ exchanger, independent of intracellular {C}a$^{2+}$ and membrane potential, by activation of the beta-receptor/adenylate-cyclase/c{AMP}-dependent cascade, resulting in suppression of transmembrane {C}a$^{2+}$ transport via the exchanger and providing for the well-documented contracture-suppressant effect of the hormone on frog heart. The beta-blocker propranolol blocks the isoproterenol effect, whereas forskolin, c{AMP}, and theophylline mimic it. In the frog heart where contractile {C}a$^{2+}$ is transported primarily by the {N}a$^{+}$-{C}a$^{2+}$ exchanger, the beta-agonists' simultaneous enhancement of {C}a$^{2+}$ current, ICa, and suppression of {N}a$^{+}$-{C}a$^{2+}$ exchanger current, INa-Ca would enable the myocyte to develop force rapidly at the onset of depolarization (enhancement of ICa) and to decrease {C}a$^{2+}$ influx (suppression of INa-Ca) later in the action potential. This unique adrenergically induced shift in the {C}a$^{2+}$ influx pathways may have evolved in response to paucity of the sarcoplasmic reticulum {C}a$^{2+}$-ATPase/phospholamban complex and absence of significant intracellular {C}a$^{2+}$ release pools in the frog heart.}, added-at = {2009-06-03T11:20:58.000+0200}, author = {Fan, J. and Shuba, Y. M. and Morad, M.}, biburl = {https://www.bibsonomy.org/bibtex/2a8af72274eb2159693424dc6a765f135/hake}, description = {The whole bibliography file I use.}, file = {Fan_1996_5527.pdf:Fan_1996_5527.pdf:PDF}, interhash = {82f593f3e1c6850dc050fa4a91da1434}, intrahash = {a8af72274eb2159693424dc6a765f135}, journal = {Proc. Natl. Acad. Sci. U. S. A.}, key = 45, keywords = {8-Bromo 8643609 AMP, ATPase, Action Adenosine Adenylate Adrenergic Adrenergic, Animals, Calcium, Carrier Comparative Contraction, Cyclase, Cyclic Exchanger, Forskolin, Gov't, Heart Heart, In Isoproterenol, Kinetics, Membrane Monophosphate, Myocardial Nickel, Non-U.S. P.H.S., Patch-Clamp Potentials, Propranolol, Proteins, Rana Receptors, Research Reticulum, Sarcoplasmic Sodium-Calcium Study, Support, Techniques, Theophylline, U.S. Ventricles, Vitro, beta, beta-Agonists, beta-Antagonists, pipiens, {C}a$^{2+}$-Transporting}, month = May, number = 11, pages = {5527-32}, timestamp = {2009-06-03T11:21:11.000+0200}, title = {Regulation of cardiac sodium-calcium exchanger by beta-adrenergic agonists.}, volume = 93, year = 1996 }