%0 Journal Article %1 Shan_2001_7195 %A Shannon, T. R. %A Chu, G. %A Kranias, E. G. %A Bers, D. M. %D 2001 %J J. Biol. Chem. %K 11087739 AMP-Dependent ATPase, Action Activation, Adenosine Adrenergic Allosteric Animals, Binding, Biological Biological, Caffeine, Calcium Calcium, Calcium-Binding Cardiac, Cardiovascular, Catalytic Cell Cells, Channels, Computer Congestive, Contraction, Cultured, Cyclic Cytosol, Diastole, Dogs, Domain, Electric Enzyme Exchanger, Factors, Failure, Ferrets, Fibers, Gov't, Heart Heart, Humans, Hydrolysis, Inhibitors, Intracellular Ion Isoproterenol, Kinases, Kinetics, Knockout, Membrane Membrane, Membranes, Mice, Microsomes, Models, Muscle Mutagenesis, Myocardial Myocardium, Myocytes, Nickel, Non-U.S. P.H.S., Phosphorylation, Potentials, Protein Proteins, Rabbits, Red, Regulation, Research Reticulum, Ruthenium Sarcoplasmic Signaling, Simulation, Sodium-Calcium Stimulation, Support, Tetracaine, Thapsigargin, Thermodynamics, Time Transport, Triphosphate, U.S. Ventricles, beta-Agonists, {C}a$^{2+}$-Transporting %N 10 %P 7195--7201 %R 10.1074/jbc.M007085200 %T Phospholamban decreases the energetic efficiency of the sarcoplasmic reticulum Ca pump. %U http://dx.doi.org/10.1074/jbc.M007085200 %V 276 %X We tested the hypothesis that increased Sarcoplasmic reticulum (SR) Ca content (Ca(SRT)) in phospholamban knockout mice (PLB-KO) is because of increased SR Ca pump efficiency defined by the steady-state SR Ca gradient. The time course of thapsigargin-sensitive ATP-dependent (45)Ca influx into and efflux out of cardiac SR vesicles from PLB-KO and wild-type (WT) mice was measured at 100 nm free Ca. We found that PLB decreased the initial SR Ca uptake rate (0.13 versus 0.31 nmol/mg/s) and decreased steady-state (45)Ca content (0.9 versus 4.1 nmol/mg protein). Furthermore, at similar total SR Ca, the pump-mediated Ca efflux rate was higher in WT (0.065 versus 0.037 nmol/mg/s). The pump-independent leak rate constant (k(leak)) was also measured at 100 nm free Ca. The results indicate that k(leak) was < 1\% of pump-mediated backflux and was not different among nonpentameric mutant PLB (PLB-C41F), WT pentameric PLB (same expression level), and PLB-KO. Therefore differences in passive SR Ca leak cannot be the cause of the higher thapsigargin-sensitive Ca efflux from the WT membranes. We conclude that the decreased total SR Ca in WT mice is caused by decreased SR Ca influx rate, an increased Ca-pump backflux, and unaltered leak. Based upon both thermodynamic and kinetic analysis, we conclude that PLB decreases the energetic efficiency of the SR Ca pump.

@article{Shan_2001_7195, abstract = {We tested the hypothesis that increased Sarcoplasmic reticulum (SR) Ca content ([Ca]({SRT})) in phospholamban knockout mice (PLB-KO) is because of increased SR Ca pump efficiency defined by the steady-state SR [Ca] gradient. The time course of thapsigargin-sensitive ATP-dependent (45)Ca influx into and efflux out of cardiac SR vesicles from PLB-KO and wild-type (WT) mice was measured at 100 nm free [Ca]. We found that PLB decreased the initial SR Ca uptake rate (0.13 versus 0.31 nmol/mg/s) and decreased steady-state (45)Ca content (0.9 versus 4.1 nmol/mg protein). Furthermore, at similar total SR [Ca], the pump-mediated Ca efflux rate was higher in WT (0.065 versus 0.037 nmol/mg/s). The pump-independent leak rate constant (k(leak)) was also measured at 100 nm free [Ca]. The results indicate that k(leak) was < 1\% of pump-mediated backflux and was not different among nonpentameric mutant PLB (PLB-C41F), WT pentameric PLB (same expression level), and PLB-KO. Therefore differences in passive SR Ca leak cannot be the cause of the higher thapsigargin-sensitive Ca efflux from the WT membranes. We conclude that the decreased total SR [Ca] in WT mice is caused by decreased SR Ca influx rate, an increased Ca-pump backflux, and unaltered leak. Based upon both thermodynamic and kinetic analysis, we conclude that PLB decreases the energetic efficiency of the SR Ca pump.}, added-at = {2009-06-03T11:20:58.000+0200}, author = {Shannon, T. R. and Chu, G. and Kranias, E. G. and Bers, D. M.}, biburl = {https://www.bibsonomy.org/bibtex/24ab608e48305d4d1bdd4fcb3bea1db3d/hake}, description = {The whole bibliography file I use.}, doi = {10.1074/jbc.M007085200}, file = {Shan_2001_7195.pdf:Shan_2001_7195.pdf:PDF}, interhash = {7404778986bf0bba5dde5251a1b034ec}, intrahash = {4ab608e48305d4d1bdd4fcb3bea1db3d}, journal = {J. Biol. Chem.}, key = 104, keywords = {11087739 AMP-Dependent ATPase, Action Activation, Adenosine Adrenergic Allosteric Animals, Binding, Biological Biological, Caffeine, Calcium Calcium, Calcium-Binding Cardiac, Cardiovascular, Catalytic Cell Cells, Channels, Computer Congestive, Contraction, Cultured, Cyclic Cytosol, Diastole, Dogs, Domain, Electric Enzyme Exchanger, Factors, Failure, Ferrets, Fibers, Gov't, Heart Heart, Humans, Hydrolysis, Inhibitors, Intracellular Ion Isoproterenol, Kinases, Kinetics, Knockout, Membrane Membrane, Membranes, Mice, Microsomes, Models, Muscle Mutagenesis, Myocardial Myocardium, Myocytes, Nickel, Non-U.S. P.H.S., Phosphorylation, Potentials, Protein Proteins, Rabbits, Red, Regulation, Research Reticulum, Ruthenium Sarcoplasmic Signaling, Simulation, Sodium-Calcium Stimulation, Support, Tetracaine, Thapsigargin, Thermodynamics, Time Transport, Triphosphate, U.S. Ventricles, beta-Agonists, {C}a$^{2+}$-Transporting}, month = Mar, number = 10, pages = {7195--7201}, pii = {M007085200}, pmid = {11087739}, timestamp = {2009-06-03T11:21:29.000+0200}, title = {Phospholamban decreases the energetic efficiency of the sarcoplasmic reticulum Ca pump.}, url = {http://dx.doi.org/10.1074/jbc.M007085200}, volume = 276, year = 2001 }