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.
%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
}