%0 Journal Article %1 Desp_2002_133 %A Despa, Sanda %A Islam, Mohammed A %A Pogwizd, Steven M %A Bers, Donald M %D 2002 %J J. Physiol. %K 11850496 ATPase, Action Active, Adaptation, After Animal, Animals, Antiporter, Benzofurans, Biological Biological, Blockers, Calcium, Calibration, Capacitance, Cardiac, Cell Cells, Channel Channels, Comparative Computer Concentration, Congestive, Contraction, Cultured, Cyclic, Diastole, Diffusion, Disease Distribution, Dyes, Electric Energy Ethers, Exchanger, Failure, Fluid, Fluorescence Fluorescence, Fluorescent Gov't, Heart In Intracellular Membrane Membranes, Microscopy, Models, Multiphoton, Muscle Myocardial Myocardium, Myocytes, Nickel, Non-U.S. Osmolar 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 Pt 1 %P 133--143 %T Intracellular Na$^+$ and Na$^+$ pump rate in rat and rabbit ventricular myocytes. %U http://jp.physoc.org/cgi/content/full/539/1/133 %V 539 %X Intracellular Na$^+$ (Na$^+$i) is centrally involved in regulation of cardiac Ca$^2+$ and contractility via Na$^+$-Ca$^2+$ exchange (NCX) and Na$^+$-H$^+$ exchange (NHX). Previous work has indicated that Na$^+$i is higher in rat than rabbit ventricular myocytes. This has major functional consequences, but the reason for the higher Na$^+$i in rat is unknown. Here, resting Na$^+$i was measured using the fluorescent indicator SBFI, with both traditional calibration and a novel null-point method (which circumvents many limitations of prior methods). In rabbit, resting Na$^+$i was 4.5 +/- 0.4 mM (traditional calibration) and 4.4 mM (null-point). Resting Na$^+$i in rat was significantly higher using both the traditional calibration (11.1 +/- 0.7 mM) and the null-point approach (11.2 mM). The rate of Na$^+$ transport by the Na$^+$ pump was measured as a function of Na$^+$i in intact cells. Rat cells exhibited a higher V(max) than rabbit (7.7 +/- 1.1 vs. 4.0 +/- 0.5 mM x min(-1)) and a higher K(m) (10.2 +/- 1.2 vs. 7.5 +/- 1.1 mM). This results in little difference in pump activity for a given Na$^+$i below 10 mM, but at measured resting Na$^+$i levels the pump-mediated Na$^+$ efflux is much higher in rat. Thus, Na$^+$ pump rate cannot explain the higher Na$^+$i in rat. Resting Na$^+$ influx rate was two to four times higher in rat, and this accounts for the higher resting Na$^+$i. Using tetrodotoxin, HOE-642 and Ni2+ to block Na$^+$ channels, NHX and NCX, respectively, we found that all three pathways may contribute to the higher resting Na$^+$ influx in rat (albeit differentially). We conclude that resting Na$^+$i is higher in rat than in rabbit, that this is caused by higher resting Na$^+$ influx in rat and that a higher Na$^+$,K$^+$-ATPase pumping rate in rat is a consequence of the higher Na$^+$i.

@article{Desp_2002_133, abstract = {Intracellular [{N}a$^{+}$] ([{N}a$^{+}$]i) is centrally involved in regulation of cardiac {C}a$^{2+}$ and contractility via {N}a$^{+}$-{C}a$^{2+}$ exchange (NCX) and {N}a$^{+}$-{H}$^+$ exchange ({NHX}). Previous work has indicated that [{N}a$^{+}$]i is higher in rat than rabbit ventricular myocytes. This has major functional consequences, but the reason for the higher [{N}a$^{+}$]i in rat is unknown. Here, resting [{N}a$^{+}$]i was measured using the fluorescent indicator SBFI, with both traditional calibration and a novel null-point method (which circumvents many limitations of prior methods). In rabbit, resting [{N}a$^{+}$]i was 4.5 +/- 0.4 mM (traditional calibration) and 4.4 mM (null-point). Resting [{N}a$^{+}$]i in rat was significantly higher using both the traditional calibration (11.1 +/- 0.7 mM) and the null-point approach (11.2 mM). The rate of {N}a$^{+}$ transport by the {N}a$^{+}$ pump was measured as a function of [{N}a$^{+}$]i in intact cells. Rat cells exhibited a higher V(max) than rabbit (7.7 +/- 1.1 vs. 4.0 +/- 0.5 mM x min(-1)) and a higher K(m) (10.2 +/- 1.2 vs. 7.5 +/- 1.1 mM). This results in little difference in pump activity for a given [{N}a$^{+}$]i below 10 mM, but at measured resting [{N}a$^{+}$]i levels the pump-mediated {N}a$^{+}$ efflux is much higher in rat. Thus, {N}a$^{+}$ pump rate cannot explain the higher [{N}a$^{+}$]i in rat. Resting {N}a$^{+}$ influx rate was two to four times higher in rat, and this accounts for the higher resting [{N}a$^{+}$]i. Using tetrodotoxin, {HOE}-642 and Ni2+ to block {N}a$^{+}$ channels, {NHX} and NCX, respectively, we found that all three pathways may contribute to the higher resting {N}a$^{+}$ influx in rat (albeit differentially). We conclude that resting [{N}a$^{+}$]i is higher in rat than in rabbit, that this is caused by higher resting {N}a$^{+}$ influx in rat and that a higher {N}a$^{+}$,{K}$^{+}$-ATPase pumping rate in rat is a consequence of the higher [{N}a$^{+}$]i.}, added-at = {2009-06-03T11:20:58.000+0200}, author = {Despa, Sanda and Islam, Mohammed A and Pogwizd, Steven M and Bers, Donald M}, biburl = {https://www.bibsonomy.org/bibtex/279db9195d61a8530a36a1e09595f1d7f/hake}, description = {The whole bibliography file I use.}, file = {Desp_2002_133.pdf:Desp_2002_133.pdf:PDF}, interhash = {c88020dfd5bf6621830acb649fa20839}, intrahash = {79db9195d61a8530a36a1e09595f1d7f}, journal = {J. Physiol.}, key = 63, keywords = {11850496 ATPase, Action Active, Adaptation, After Animal, Animals, Antiporter, Benzofurans, Biological Biological, Blockers, Calcium, Calibration, Capacitance, Cardiac, Cell Cells, Channel Channels, Comparative Computer Concentration, Congestive, Contraction, Cultured, Cyclic, Diastole, Diffusion, Disease Distribution, Dyes, Electric Energy Ethers, Exchanger, Failure, Fluid, Fluorescence Fluorescence, Fluorescent Gov't, Heart In Intracellular Membrane Membranes, Microscopy, Models, Multiphoton, Muscle Myocardial Myocardium, Myocytes, Nickel, Non-U.S. Osmolar 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 = Feb, number = {Pt 1}, pages = {133--143}, pii = {PHY_12940}, pmid = {11850496}, timestamp = {2009-06-03T11:21:10.000+0200}, title = {Intracellular [{N}a$^{+}$] and {N}a$^{+}$ pump rate in rat and rabbit ventricular myocytes.}, url = {http://jp.physoc.org/cgi/content/full/539/1/133}, volume = 539, year = 2002 }