%0 Journal Article %1 Hoba_2000_690 %A Hobai, I. A. %A O'Rourke, B. %D 2000 %J Circ. Res. %K 11029397 Animal, Animals, Artificial, Buffers, Caffeine, Calcium, Cardiac Cells, Congestive, Cultured, Disease Dogs, Electric Enzyme Exchanger, Failure, Female, Gov't, Heart Inhibitors, Ion Male, Membrane Models, Myocardium, Nickel, P.H.S., Pacing, Phosphodiesterase Potentials, Research Reticulum, Sarcoplasmic Sodium-Calcium Stimulation, Support, Thapsigargin, Transport, U.S. %N 8 %P 690-8 %T Enhanced Ca$^2+$-activated Na$^+$-Ca$^2+$ exchange activity in canine pacing-induced heart failure. %U http://circres.ahajournals.org/cgi/content/full/87/8/690 %V 87 %X Defective excitation-contraction coupling in heart failure is generally associated with both a reduction in sarcoplasmic reticulum (SR) Ca$^2+$ uptake and a greater dependence on transsarcolemmal Na$^+$-Ca$^2+$ exchange (NCX) for Ca$^2+$ removal. Although a relative increase in NCX is expected when SR function is impaired, few and contradictory studies have addressed whether there is an absolute increase in NCX activity. The present study examines in detail NCX density and function in left ventricular midmyocardial myocytes isolated from normal or tachycardic pacing-induced failing canine hearts. No change of NCX current density was evident in myocytes from failing hearts when intracellular Ca$^2+$ (Ca$^2+$(i)) was buffered to 200 nmol/L. However, when Ca$^2+$(i) was minimally buffered with 50 micromol/L indo-1, Ca$^2+$ extrusion via NCX during caffeine application was doubled in failing versus normal cells. In other voltage-clamp experiments in which SR uptake was blocked with thapsigargin, both reverse-mode and forward-mode NCX currents and Ca$^2+$ transport were increased >2-fold in failing cells. These results suggest that, in addition to a relative increase in NCX function as a consequence of defective SR Ca$^2+$ uptake, there is an absolute increase in NCX function that depends on Ca$^2+$(i) in the failing heart.

@article{Hoba_2000_690, abstract = {Defective excitation-contraction coupling in heart failure is generally associated with both a reduction in sarcoplasmic reticulum (SR) {C}a$^{2+}$ uptake and a greater dependence on transsarcolemmal {N}a$^{+}$-{C}a$^{2+}$ exchange (NCX) for {C}a$^{2+}$ removal. Although a relative increase in NCX is expected when SR function is impaired, few and contradictory studies have addressed whether there is an absolute increase in NCX activity. The present study examines in detail NCX density and function in left ventricular midmyocardial myocytes isolated from normal or tachycardic pacing-induced failing canine hearts. No change of NCX current density was evident in myocytes from failing hearts when intracellular {C}a$^{2+}$ ([{C}a$^{2+}$](i)) was buffered to 200 nmol/L. However, when [{C}a$^{2+}$](i) was minimally buffered with 50 micromol/L indo-1, {C}a$^{2+}$ extrusion via NCX during caffeine application was doubled in failing versus normal cells. In other voltage-clamp experiments in which SR uptake was blocked with thapsigargin, both reverse-mode and forward-mode NCX currents and {C}a$^{2+}$ transport were increased >2-fold in failing cells. These results suggest that, in addition to a relative increase in NCX function as a consequence of defective SR {C}a$^{2+}$ uptake, there is an absolute increase in NCX function that depends on [{C}a$^{2+}$](i) in the failing heart.}, added-at = {2009-06-03T11:20:58.000+0200}, author = {Hobai, I. A. and O'Rourke, B.}, biburl = {https://www.bibsonomy.org/bibtex/2a19bebd6e47a1fe0f41b7656218fabc0/hake}, description = {The whole bibliography file I use.}, file = {Hoba_2000_690.pdf:Hoba_2000_690.pdf:PDF}, interhash = {23383f12339c0fcfe13ab613bb146c67}, intrahash = {a19bebd6e47a1fe0f41b7656218fabc0}, journal = {Circ. Res.}, keywords = {11029397 Animal, Animals, Artificial, Buffers, Caffeine, Calcium, Cardiac Cells, Congestive, Cultured, Disease Dogs, Electric Enzyme Exchanger, Failure, Female, Gov't, Heart Inhibitors, Ion Male, Membrane Models, Myocardium, Nickel, P.H.S., Pacing, Phosphodiesterase Potentials, Research Reticulum, Sarcoplasmic Sodium-Calcium Stimulation, Support, Thapsigargin, Transport, U.S.}, month = Oct, number = 8, pages = {690-8}, timestamp = {2009-06-03T11:21:15.000+0200}, title = {Enhanced {C}a$^{2+}$-activated {N}a$^{+}$-{C}a$^{2+}$ exchange activity in canine pacing-induced heart failure.}, url = {http://circres.ahajournals.org/cgi/content/full/87/8/690}, volume = 87, year = 2000 }