%0 Journal Article %1 Desp_2002_2543 %A Despa, Sanda %A Islam, Mohammed A %A Weber, Christopher R %A Pogwizd, Steven M %A Bers, Donald M %D 2002 %J Circulation %K 12034663 ATPase, Action Active, Adaptation, After Animal, Animals, Antiporter, Biological Biological, Blockers, Calcium, Capacitance, Cardiac, Cell Cells, Channel Channels, Comparative Computer Congestive, Contraction, Cultured, Diastole, Diffusion, Disease Distribution, Electric Energy Exchanger, Failure, Fluid, Fluorescence Fluorescence, Gov't, Heart In Intracellular Membrane Microscopy, Models, Multiphoton, Muscle Myocardial Myocardium, Myocytes, Nickel, Non-U.S. P.H.S., Patch-Clamp Photobleaching, Physiological, Potenti, Potentials, Rabbits, Rats, Recovery Research Resonance Sarcolemma, Separation, Simulation, Size, Sodium Sodium, Sodium-Calcium Sodium-Hydrogen Space, Stimulation, Strophanthidin, Study, Support, Techniques, Tetrodotoxin, Tissue Transfer, Transport, U.S. Ventricles, Vitro, als, {N}a$^{+}$-{K}$^{+}$-Exchanging %N 21 %P 2543--2548 %T Intracellular Na$^+$ concentration is elevated in heart failure but Na/K pump function is unchanged. %U http://circ.ahajournals.org/cgi/reprint/105/21/2543.pdf %V 105 %X BACKGROUND: Intracellular sodium concentration (Na$^+$(i)) modulates cardiac contractile and electrical activity through Na/Ca exchange (NCX). Upregulation of NCX in heart failure (HF) may magnify the functional impact of altered Na$^+$(i). METHODS AND RESULTS: We measured Na$^+$(i) by using sodium binding benzofuran isophthalate in control and HF rabbit ventricular myocytes (HF induced by aortic insufficiency and constriction). Resting Na$^+$(i) was 9.7+/-0.7 versus 6.6+/-0.5 mmol/L in HF versus control. In both cases, Na$^+$(i) increased by approximately 2 mmol/L when myocytes were stimulated (0.5 to 3 Hz). To identify the mechanisms responsible for Na$^+$(i) elevation in HF, we measured the Na$^+$(i) dependence of Na/K pump-mediated Na$^+$ extrusion. There was no difference in V(max) (8.3+/-0.7 versus 8.0+/-0.8 mmol/L/min) or K(m) (9.2+/-1.0 versus 9.9+/-0.8 mmol/L in HF and control, respectively). Therefore, at measured Na$^+$(i) levels, the Na/K pump rate is actually higher in HF. However, resting Na$^+$ influx was twice as high in HF versus control (2.3+/-0.3 versus 1.1+/-0.2 mmol/L/min), primarily the result of a tetrodotoxin-sensitive pathway. CONCLUSIONS: Myocyte Na$^+$(i) is elevated in HF as a result of higher diastolic Na$^+$ influx (with unaltered Na/K-ATPase characteristics). In HF, the combined increased Na$^+$(i), decreased Ca$^2+$ transient, and prolonged action potential all profoundly affect cellular Ca$^2+$ regulation, promoting greater Ca$^2+$ influx through NCX during action potentials. Notably, the elevated Na$^+$(i) may be critical in limiting the contractile dysfunction observed in HF.

@article{Desp_2002_2543, abstract = {BACKGROUND: Intracellular sodium concentration ([{N}a$^{+}$](i)) modulates cardiac contractile and electrical activity through Na/Ca exchange (NCX). Upregulation of NCX in heart failure (HF) may magnify the functional impact of altered [{N}a$^{+}$](i). METHODS {AND} RESULTS: We measured [{N}a$^{+}$](i) by using sodium binding benzofuran isophthalate in control and HF rabbit ventricular myocytes (HF induced by aortic insufficiency and constriction). Resting [{N}a$^{+}$](i) was 9.7+/-0.7 versus 6.6+/-0.5 mmol/L in HF versus control. In both cases, [{N}a$^{+}$](i) increased by approximately 2 mmol/L when myocytes were stimulated (0.5 to 3 Hz). To identify the mechanisms responsible for [{N}a$^{+}$](i) elevation in HF, we measured the [{N}a$^{+}$](i) dependence of Na/K pump-mediated {N}a$^{+}$ extrusion. There was no difference in V(max) (8.3+/-0.7 versus 8.0+/-0.8 mmol/L/min) or K(m) (9.2+/-1.0 versus 9.9+/-0.8 mmol/L in HF and control, respectively). Therefore, at measured [{N}a$^{+}$](i) levels, the Na/K pump rate is actually higher in HF. However, resting {N}a$^{+}$ influx was twice as high in HF versus control (2.3+/-0.3 versus 1.1+/-0.2 mmol/L/min), primarily the result of a tetrodotoxin-sensitive pathway. {CONCLUSIONS}: Myocyte [{N}a$^{+}$](i) is elevated in HF as a result of higher diastolic {N}a$^{+}$ influx (with unaltered Na/K-ATPase characteristics). In HF, the combined increased [{N}a$^{+}$](i), decreased {C}a$^{2+}$ transient, and prolonged action potential all profoundly affect cellular {C}a$^{2+}$ regulation, promoting greater {C}a$^{2+}$ influx through NCX during action potentials. Notably, the elevated [{N}a$^{+}$](i) may be critical in limiting the contractile dysfunction observed in HF.}, added-at = {2009-06-03T11:20:58.000+0200}, author = {Despa, Sanda and Islam, Mohammed A and Weber, Christopher R and Pogwizd, Steven M and Bers, Donald M}, biburl = {https://www.bibsonomy.org/bibtex/21a331fd60975951b267eab07c4cdc396/hake}, description = {The whole bibliography file I use.}, file = {Desp_2002_2543.pdf:Desp_2002_2543.pdf:PDF}, interhash = {fb43a0ebe1ff451c1463d3b098bafa02}, intrahash = {1a331fd60975951b267eab07c4cdc396}, journal = {Circulation}, key = 64, keywords = {12034663 ATPase, Action Active, Adaptation, After Animal, Animals, Antiporter, Biological Biological, Blockers, Calcium, Capacitance, Cardiac, Cell Cells, Channel Channels, Comparative Computer Congestive, Contraction, Cultured, Diastole, Diffusion, Disease Distribution, Electric Energy Exchanger, Failure, Fluid, Fluorescence Fluorescence, Gov't, Heart In Intracellular Membrane Microscopy, Models, Multiphoton, Muscle Myocardial Myocardium, Myocytes, Nickel, Non-U.S. P.H.S., Patch-Clamp Photobleaching, Physiological, Potenti, Potentials, Rabbits, Rats, Recovery Research Resonance Sarcolemma, Separation, Simulation, Size, Sodium Sodium, Sodium-Calcium Sodium-Hydrogen Space, Stimulation, Strophanthidin, Study, Support, Techniques, Tetrodotoxin, Tissue Transfer, Transport, U.S. Ventricles, Vitro, als, {N}a$^{+}$-{K}$^{+}$-Exchanging}, month = May, number = 21, pages = {2543--2548}, pmid = {12034663}, timestamp = {2009-06-03T11:21:10.000+0200}, title = {Intracellular {N}a$^{+}$ concentration is elevated in heart failure but Na/K pump function is unchanged.}, url = {http://circ.ahajournals.org/cgi/reprint/105/21/2543.pdf}, volume = 105, year = 2002 }