%0 Journal Article %1 Song_2001_794 %A Song, L. S. %A Wang, S. Q. %A Xiao, R. P. %A Spurgeon, H. %A Lakatta, E. G. %A Cheng, H. %D 2001 %J Circ. Res. %K 11325871 Action Adrenergic, Agents, Aggregation, Agonists, Aniline Animals, C, Calcium Calcium, Cell Cells, Channel, Channels, Chloride, Compounds, Contraction, Cross-Talk, Cultured, Cytoplasmic Dose-Response Drug, Dyes, Enzyme Fluid, Fluorescent Gov't, Immunohistochemistry, Inhibitors, Intracellular L-Type, Methacholine Musca, Muscarinic, Myocardial Myocardium, Non-U.S. Norepinephrine, Nuclear, Oligodendroglia, Oxazoles, P.H.S., P1, Patch-Clamp Phospholipase Potentials, Purinergic Rats, Reaction Receptor Receptors, Relationship, Release Research Reticulum, Ryanodine Sarcoplasmic Separation, Signaling, Sprague-Dawley, Stem Support, Techniques, Theobromine, Time, U.S. Vasoconstrictor Xanthenes, alpha-1, and beta, rinic %N 8 %P 794--801 %T $\beta$-Adrenergic stimulation synchronizes intracellular Ca$^2+$ release during excitation-contraction coupling in cardiac myocytes. %U http://circres.ahajournals.org/cgi/content/full/88/8/794 %V 88 %X To elucidate microscopic mechanisms underlying the modulation of cardiac excitation-contraction (EC) coupling by beta-adrenergic receptor (beta-AR) stimulation, we examined local Ca$^2+$ release function, ie, Ca$^2+$ spikes at individual transverse tubule-sarcoplasmic reticulum (T-SR) junctions, using confocal microscopy and our recently developed technique for release flux measurement. beta-AR stimulation by norepinephrine plus an alpha(1)-adrenergic blocker, prazosin, increased the amplitude of SR Ca$^2+$ release flux (J(SR)), its running integral (integralJ(SR)), and L-type Ca$^2+$ channel current (I(Ca)), and it shifted their bell-shaped voltage dependence leftward by approximately 10 mV, with the relative effects ranking I(Ca)> J(SR)>integralJ(SR). Confocal imaging revealed that the bell-shaped voltage dependence of SR Ca$^2+$ release is attributable to a graded recruitment of T-SR junctions as well as to changes in Ca$^2+$ spike amplitudes. beta-AR stimulation increased the fractional T-SR junctions that fired Ca$^2+$ spikes and augmented Ca$^2+$ spike amplitudes, without altering the SR Ca$^2+$ load, suggesting that more release units were activated synchronously among and within T-SR junctions. Moreover, beta-AR stimulation decreased the latency and temporal dispersion of Ca$^2+$ spike occurrence at a given voltage, delivering most of the Ca$^2+$ at the onset of depolarization rather than spreading it out throughout depolarization. Because the synchrony of Ca$^2+$ spikes affects Ca$^2+$ delivery per unit of time to contractile myofilaments, and because the myofilaments display a steep Ca$^2+$ dependence, our data suggest that synchronization of SR Ca$^2+$ release represents a heretofore unappreciated mechanism of beta-AR modulation of cardiac inotropy.

@article{Song_2001_794, abstract = {To elucidate microscopic mechanisms underlying the modulation of cardiac excitation-contraction (EC) coupling by beta-adrenergic receptor (beta-AR) stimulation, we examined local {C}a$^{2+}$ release function, ie, {C}a$^{2+}$ spikes at individual transverse tubule-sarcoplasmic reticulum (T-SR) junctions, using confocal microscopy and our recently developed technique for release flux measurement. beta-AR stimulation by norepinephrine plus an alpha(1)-adrenergic blocker, prazosin, increased the amplitude of SR {C}a$^{2+}$ release flux (J(SR)), its running integral (integralJ(SR)), and L-type {C}a$^{2+}$ channel current (I(Ca)), and it shifted their bell-shaped voltage dependence leftward by approximately 10 mV, with the relative effects ranking I(Ca)> J(SR)>integralJ(SR). Confocal imaging revealed that the bell-shaped voltage dependence of SR {C}a$^{2+}$ release is attributable to a graded recruitment of T-SR junctions as well as to changes in {C}a$^{2+}$ spike amplitudes. beta-AR stimulation increased the fractional T-SR junctions that fired {C}a$^{2+}$ spikes and augmented {C}a$^{2+}$ spike amplitudes, without altering the SR {C}a$^{2+}$ load, suggesting that more release units were activated synchronously among and within T-SR junctions. Moreover, beta-AR stimulation decreased the latency and temporal dispersion of {C}a$^{2+}$ spike occurrence at a given voltage, delivering most of the {C}a$^{2+}$ at the onset of depolarization rather than spreading it out throughout depolarization. Because the synchrony of {C}a$^{2+}$ spikes affects {C}a$^{2+}$ delivery per unit of time to contractile myofilaments, and because the myofilaments display a steep {C}a$^{2+}$ dependence, our data suggest that synchronization of SR {C}a$^{2+}$ release represents a heretofore unappreciated mechanism of beta-AR modulation of cardiac inotropy.}, added-at = {2009-06-03T11:20:58.000+0200}, author = {Song, L. S. and Wang, S. Q. and Xiao, R. P. and Spurgeon, H. and Lakatta, E. G. and Cheng, H.}, biburl = {https://www.bibsonomy.org/bibtex/2483a6ff9f9745e4b9241a852fd301759/hake}, description = {The whole bibliography file I use.}, file = {Song_2001_794.pdf:Song_2001_794.pdf:PDF}, interhash = {e276ed049d8be47b76d1b251ac271f45}, intrahash = {483a6ff9f9745e4b9241a852fd301759}, journal = {Circ. Res.}, keywords = {11325871 Action Adrenergic, Agents, Aggregation, Agonists, Aniline Animals, C, Calcium Calcium, Cell Cells, Channel, Channels, Chloride, Compounds, Contraction, Cross-Talk, Cultured, Cytoplasmic Dose-Response Drug, Dyes, Enzyme Fluid, Fluorescent Gov't, Immunohistochemistry, Inhibitors, Intracellular L-Type, Methacholine Musca, Muscarinic, Myocardial Myocardium, Non-U.S. Norepinephrine, Nuclear, Oligodendroglia, Oxazoles, P.H.S., P1, Patch-Clamp Phospholipase Potentials, Purinergic Rats, Reaction Receptor Receptors, Relationship, Release Research Reticulum, Ryanodine Sarcoplasmic Separation, Signaling, Sprague-Dawley, Stem Support, Techniques, Theobromine, Time, U.S. Vasoconstrictor Xanthenes, alpha-1, and beta, rinic}, month = Apr, number = 8, pages = {794--801}, pmid = {11325871}, timestamp = {2009-06-03T11:21:32.000+0200}, title = {$\beta$-Adrenergic stimulation synchronizes intracellular {C}a$^{2+}$ release during excitation-contraction coupling in cardiac myocytes.}, url = {http://circres.ahajournals.org/cgi/content/full/88/8/794}, volume = 88, year = 2001 }