%0 Journal Article %1 Baar_1998_2437 %A Baartscheer, A. %A Schumacher, C. A. %A Fiolet, J. W. %D 1998 %J J Mol Cell Cardiol %K Animals; Calcium, Cytoplasm, Energy Exchanger, Heart Male; Metabolism; Rats, Rats; Sodium, Sodium-Calcium Ventricles, Wistar; metabolism metabolism; %N 11 %P 2437--2447 %R 10.1006/jmcc.1998.0803 %T Cytoplasmic sodium, calcium and free energy change of the Na+/Ca2+-exchanger in rat ventricular myocytes. %U http://dx.doi.org/10.1006/jmcc.1998.0803 %V 30 %X The relationship between changing driving force of the Na+/Ca2+-exchanger (deltaG(exch)) and associated cytosolic calcium fluxes was studied in rat ventricular myocytes. DeltaG(exch) was abruptly reversed by the reduction of extracellular sodium (Na+o) with or without sustained depolarization by the elevation of potassium (K+o). Cytosolic sodium (Na+i) and calcium (Ca2+i) were measured with SBFI and indo-1 respectively and the time course of recovery of deltaG(exch) was calculated. Following abrupt reversal of deltaG(exch) from +4.1 to -9.2 kJ/mol Na+i exponentially decreased from 9.6-2.5 mmol/l (t(1/2) about 30 s) and Ca2+i transiently increased to a peak value after about 30 s. Negative values of deltaG(exch) were associated with an increase and positive values with a decrease of Ca2+i. Equilibrium (deltaG(exch) = 0) was reached after about 30 s coinciding with the time to peak Ca2+i. After 180 s deltaG(exch) reached a new steady state at +3.5 kJ/mol. Inhibition of SR with ryanodine or thapsigargin reduced the amplitude of the Ca2+i transient and shifted its peak to 80 s, but did not affect the time course of Na+i changes. In the presence of ryanodine or thapsigargin the time required for deltaG(exch) to recover to equilibrium was also shifted to 80 s. When we changed the deltaG(exch) to the same extent by the reduction of Na+o in combination with a sustained depolarization, Na+i decreased less and the amplitude of Ca2+i transient was much enhanced. This increase of Ca2+i was completely abolished by verapamil. DeltaG(exch) only recovered to a little above equilibrium (+1 kJ/mol). Inhibition of the Na+/K+-ATPase with ouabain entirely prevented the decrease of Na+i and caused a much larger increase of Ca2+i, which remained elevated; deltaG(exch) recovered to equilibrium and never returned to positive values. The rate of change of total cytosolic calcium was related to deltaG(exch), despite the fact that the calcium flux associated with the exchanger itself contributed only about 10\%; SR related flux contributed by about 90\% to the rate of change of total cytosolic calcium. In summary, reduction of Na+o causes reversal of the Na+/Ca2+-exchanger and its driving force deltaG(exch), a transient increase of Ca2+i and a decrease of Na+i. The influx of calcium associated with reversed deltaG(exch) triggers the release of calcium from SR. Both the decrease of Na+i and the increase of Ca2+i contribute to the recovery of deltaG(exch) to equilibrium. The time at which deltaG(exch) reaches equilibrium always coincides with the time to peak of Ca2+i transient. Activation of the Na+/K+-ATPase is required to reduce Na+i and recover deltaG(exch) to positive values in order to reduce Ca2+i. We conclude that deltaG(exch) is a major regulator of cytosolic calcium by interaction with SR.

@article{Baar_1998_2437, abstract = {The relationship between changing driving force of the Na+/Ca2+-exchanger (deltaG(exch)) and associated cytosolic calcium fluxes was studied in rat ventricular myocytes. DeltaG(exch) was abruptly reversed by the reduction of extracellular sodium ([Na+]o) with or without sustained depolarization by the elevation of potassium ([K+]o). Cytosolic sodium ([Na+]i) and calcium ([Ca2+]i) were measured with SBFI and indo-1 respectively and the time course of recovery of deltaG(exch) was calculated. Following abrupt reversal of deltaG(exch) from +4.1 to -9.2 kJ/mol [Na+]i exponentially decreased from 9.6-2.5 mmol/l (t(1/2) about 30 s) and [Ca2+]i transiently increased to a peak value after about 30 s. Negative values of deltaG(exch) were associated with an increase and positive values with a decrease of [Ca2+]i. Equilibrium (deltaG(exch) = 0) was reached after about 30 s coinciding with the time to peak [Ca2+]i. After 180 s deltaG(exch) reached a new steady state at +3.5 kJ/mol. Inhibition of SR with ryanodine or thapsigargin reduced the amplitude of the [Ca2+]i transient and shifted its peak to 80 s, but did not affect the time course of [Na+]i changes. In the presence of ryanodine or thapsigargin the time required for deltaG(exch) to recover to equilibrium was also shifted to 80 s. When we changed the deltaG(exch) to the same extent by the reduction of [Na+]o in combination with a sustained depolarization, [Na+]i decreased less and the amplitude of [Ca2+]i transient was much enhanced. This increase of [Ca2+]i was completely abolished by verapamil. DeltaG(exch) only recovered to a little above equilibrium (+1 kJ/mol). Inhibition of the Na+/K+-ATPase with ouabain entirely prevented the decrease of [Na+]i and caused a much larger increase of [Ca2+]i, which remained elevated; deltaG(exch) recovered to equilibrium and never returned to positive values. The rate of change of total cytosolic calcium was related to deltaG(exch), despite the fact that the calcium flux associated with the exchanger itself contributed only about 10\%; SR related flux contributed by about 90\% to the rate of change of total cytosolic calcium. In summary, reduction of [Na+]o causes reversal of the Na+/Ca2+-exchanger and its driving force deltaG(exch), a transient increase of [Ca2+]i and a decrease of [Na+]i. The influx of calcium associated with reversed deltaG(exch) triggers the release of calcium from SR. Both the decrease of [Na+]i and the increase of [Ca2+]i contribute to the recovery of deltaG(exch) to equilibrium. The time at which deltaG(exch) reaches equilibrium always coincides with the time to peak of [Ca2+]i transient. Activation of the Na+/K+-ATPase is required to reduce [Na+]i and recover deltaG(exch) to positive values in order to reduce [Ca2+]i. We conclude that deltaG(exch) is a major regulator of cytosolic calcium by interaction with SR.}, added-at = {2009-06-03T11:20:58.000+0200}, author = {Baartscheer, A. and Schumacher, C. A. and Fiolet, J. W.}, biburl = {https://www.bibsonomy.org/bibtex/26cc86c1b8073badbf1abcecf1a8252f4/hake}, description = {The whole bibliography file I use.}, doi = {10.1006/jmcc.1998.0803}, file = {Baar_1998_2437.pdf:Baar_1998_2437.pdf:PDF}, institution = {Department of Clinical and Experimental Cardiology, Academic Medical Center, University of Amsterdam and the Interuniversity Cardiology Institute of The Netherlands.}, interhash = {3aa75f23e67c8b22bc8d5432f0cdea74}, intrahash = {6cc86c1b8073badbf1abcecf1a8252f4}, journal = {J Mol Cell Cardiol}, keywords = {Animals; Calcium, Cytoplasm, Energy Exchanger, Heart Male; Metabolism; Rats, Rats; Sodium, Sodium-Calcium Ventricles, Wistar; metabolism metabolism;}, month = Nov, number = 11, pages = {2437--2447}, pdf = {Baar_1998_2437.pdf}, pii = {S0022-2828(98)90803-3}, pmid = {9925378}, timestamp = {2009-06-03T11:21:01.000+0200}, title = {Cytoplasmic sodium, calcium and free energy change of the Na+/Ca2+-exchanger in rat ventricular myocytes.}, url = {http://dx.doi.org/10.1006/jmcc.1998.0803}, volume = 30, year = 1998 }