%0 Journal Article %1 Bers_2003_897 %A Bers, Donald M %A Barry, William H %A Despa, Sanda %D 2003 %J Cardiovasc. Res. %K 12650864 ATPase, Active, Adaptation, Animals, Antiporter, Biological Biological, Calcium, Capacitance, Cardiac, Cell Cells, Comparative Computer Cultured, Diffusion, Distribution, Electric Exchanger, Gov't, H.S., Heart Intracellular Membrane Models, Muscle Myocytes, Non-U.S. P., P.H.S., Physiological, Potentials, Rabbits, Rats, Research Sarcolemma, Simulation, Size, Sodium, Sodium-Calcium Sodium-Hydrogen Space, Study, Support, Tissue Transport, U.S. Ventricles, {N}a$^{+}$-{K}$^{+}$-Exchanging %N 4 %P 897--912 %T Intracellular Na$^+$ regulation in cardiac myocytes. %U http://dx.doi.org/10.1016/S0008-6363(02)00656-9 %V 57 %X Intracellular Na$^+$ (Na$^+$i) is regulated in cardiac myocytes by a balance of Na$^+$ influx and efflux mechanisms. In the normal cell there is a large steady state electrochemical gradient favoring Na$^+$ influx. This potential energy is used by numerous transport mechanisms, including Na$^+$ channels and transporters which couple Na$^+$ influx to either co- or counter-transport of other ions and solutes. Six sarcolemmal Na$^+$ influx pathways are discussed in relatively quantitative terms: Na$^+$ channels, Na$^+$/Ca$^2+$ exchange, Na$^+$/H$^+$ exchange, Na$^+$/Mg2+ exchange, Na$^+$/HCO3- cotransport and Na$^+$/K$^+$/2Cl$^-$ cotransport. Under normal conditions Na$^+$/Ca$^2+$ exchange and Na$^+$ channels are the dominant Na$^+$ influx pathways, but other transporters may become increasingly important during altered conditions (e.g. acidosis or cell volume stress). Mitochondria also exhibit Na$^+$/Ca$^2+$ antiporter and Na$^+$/H$^+$ exchange activity that are important in mitochondrial function. These coupled fluxes of Na$^+$ with Ca$^2+$, H$^+$ and HCO3- make the detailed understanding of Na$^+$i regulation pivotal to the understanding of both cardiac excitation-contraction coupling and pH regulation. The Na$^+$/K$^+$-ATPase is the main route for Na$^+$ extrusion from cells and Na$^+$i is a primary regulator under physiological conditions. Na$^+$i is higher in rat than rabbit ventricular myocytes and the reason appears to be higher Na$^+$ influx in rat with a consequent rise in Na$^+$/K$^+$-ATPase activity (rather than lower Na$^+$/K$^+$-ATPase function in rat). This has direct functional consequences. There may also be subcellular Na$^+$i gradients locally in ventricular myocytes and this may also have important functional implications. Thus, the balance of Na$^+$ fluxes in heart cells may be complex, but myocyte Na$^+$ regulation is functionally important and merits focused attention as in this issue.

@article{Bers_2003_897, abstract = {Intracellular [{N}a$^{+}$] ([{N}a$^{+}$]i) is regulated in cardiac myocytes by a balance of {N}a$^{+}$ influx and efflux mechanisms. In the normal cell there is a large steady state electrochemical gradient favoring {N}a$^{+}$ influx. This potential energy is used by numerous transport mechanisms, including {N}a$^{+}$ channels and transporters which couple {N}a$^{+}$ influx to either co- or counter-transport of other ions and solutes. Six sarcolemmal {N}a$^{+}$ influx pathways are discussed in relatively quantitative terms: {N}a$^{+}$ channels, {N}a$^{+}$/{C}a$^{2+}$ exchange, {N}a$^{+}$/{H}$^+$ exchange, {N}a$^{+}$/Mg2+ exchange, {N}a$^{+}$/{HCO}3- cotransport and {N}a$^{+}$/{K}$^{+}$/2{C}l$^{-}$ cotransport. Under normal conditions {N}a$^{+}$/{C}a$^{2+}$ exchange and {N}a$^{+}$ channels are the dominant {N}a$^{+}$ influx pathways, but other transporters may become increasingly important during altered conditions (e.g. acidosis or cell volume stress). Mitochondria also exhibit {N}a$^{+}$/{C}a$^{2+}$ antiporter and {N}a$^{+}$/{H}$^+$ exchange activity that are important in mitochondrial function. These coupled fluxes of {N}a$^{+}$ with {C}a$^{2+}$, {H}$^+$ and {HCO}3- make the detailed understanding of [{N}a$^{+}$]i regulation pivotal to the understanding of both cardiac excitation-contraction coupling and pH regulation. The {N}a$^{+}$/{K}$^{+}$-ATPase is the main route for {N}a$^{+}$ extrusion from cells and [{N}a$^{+}$]i is a primary regulator under physiological conditions. [{N}a$^{+}$]i is higher in rat than rabbit ventricular myocytes and the reason appears to be higher {N}a$^{+}$ influx in rat with a consequent rise in {N}a$^{+}$/{K}$^{+}$-ATPase activity (rather than lower {N}a$^{+}$/{K}$^{+}$-ATPase function in rat). This has direct functional consequences. There may also be subcellular [{N}a$^{+}$]i gradients locally in ventricular myocytes and this may also have important functional implications. Thus, the balance of {N}a$^{+}$ fluxes in heart cells may be complex, but myocyte {N}a$^{+}$ regulation is functionally important and merits focused attention as in this issue.}, added-at = {2009-06-03T11:20:58.000+0200}, author = {Bers, Donald M and Barry, William H and Despa, Sanda}, biburl = {https://www.bibsonomy.org/bibtex/217f6677202e1b77b574c3a5f7e4ce423/hake}, description = {The whole bibliography file I use.}, file = {Bers_2003_897.pdf:Bers_2003_897.pdf:PDF}, interhash = {6eff74d0e5930bf596c335de15d9e40b}, intrahash = {17f6677202e1b77b574c3a5f7e4ce423}, journal = {Cardiovasc. Res.}, key = 69, keywords = {12650864 ATPase, Active, Adaptation, Animals, Antiporter, Biological Biological, Calcium, Capacitance, Cardiac, Cell Cells, Comparative Computer Cultured, Diffusion, Distribution, Electric Exchanger, Gov't, H.S., Heart Intracellular Membrane Models, Muscle Myocytes, Non-U.S. P., P.H.S., Physiological, Potentials, Rabbits, Rats, Research Sarcolemma, Simulation, Size, Sodium, Sodium-Calcium Sodium-Hydrogen Space, Study, Support, Tissue Transport, U.S. Ventricles, {N}a$^{+}$-{K}$^{+}$-Exchanging}, month = Mar, number = 4, pages = {897--912}, pii = {S0008636302006569}, pmid = {12650864}, timestamp = {2009-06-03T11:21:03.000+0200}, title = {Intracellular {N}a$^{+}$ regulation in cardiac myocytes.}, url = {http://dx.doi.org/10.1016/S0008-6363(02)00656-9}, volume = 57, year = 2003 }