Journal article
β-Adrenergic stimulation synchronizes intracellular Ca2+ release during excitation-contraction coupling in cardiac myocytes
Circulation research, Vol.88(8), pp.794-801
2001
DOI: 10.1161/hh0801.090461
PMID: 11325871
Abstract
To elucidate microscopic mechanisms underlying the modulation of cardiac excitation-contraction (EC) coupling by β-adrenergic receptor (β-AR) stimulation, we examined local Ca2+ release function, ie, Ca2+ spikes at individual transverse tubule-sarcoplasmic reticulum (T-SR) junctions, using confocal microscopy and our recently developed technique for release flux measurement. β-AR stimulation by norepinephrine plus an α1-adrenergic blocker, prazosin, increased the amplitude of SR Ca2+ release flux (JSR), its running integral (∫JSR), and L-type Ca2+ channel current (ICa, and it shifted their bell-shaped voltage dependence leftward by ≈ 10 mV, with the relative effects ranking ICa> JSR>∫JSR. Confocal imaging revealed that the bell-shaped voltage dependence of SR Ca2+ release is attributable to a graded recruitment of T-SR junctions as well as to changes in Ca2+ spike amplitudes. β-AR stimulation increased the fractional T-SR junctions that fired Ca2+ spikes and augmented Ca2+ spike amplitudes, without altering the SR Ca2+ load, suggesting that more release units were activated synchronously among and within T-SR junctions. Moreover, β-AR stimulation decreased the latency and temporal dispersion of Ca2+ spike occurrence at a given voltage, delivering most of the Ca2+ at the onset of depolarization rather than spreading it out throughout depolarization. Because the synchrony of Ca2+ spikes affects Ca2+ delivery per unit of time to contractile myofilaments, and because the: myofilaments display a steep Ca2+ dependence, our data suggest that synchronization of SR Ca2+ release represents a heretofore unappreciated mechanism of β-AR modulation of cardiac inotropy.
Details
- Title: Subtitle
- β-Adrenergic stimulation synchronizes intracellular Ca2+ release during excitation-contraction coupling in cardiac myocytes
- Creators
- Long-Sheng SONG - Laboratory of Cardiovascular Sciences, National Institute on Aging, National Institutes of Health, Baltimore, Md, ChinaShi-Qiang WANG - Laboratory of Cardiovascular Sciences, National Institute on Aging, National Institutes of Health, Baltimore, Md, ChinaRui-Ping XIAO - Laboratory of Cardiovascular Sciences, National Institute on Aging, National Institutes of Health, Baltimore, Md, ChinaHarold SPURGEON - Laboratory of Cardiovascular Sciences, National Institute on Aging, National Institutes of Health, Baltimore, Md, ChinaEdward G LAKATTA - Laboratory of Cardiovascular Sciences, National Institute on Aging, National Institutes of Health, Baltimore, Md, ChinaHEPING CHENG - Laboratory of Cardiovascular Sciences, National Institute on Aging, National Institutes of Health, Baltimore, Md, China
- Resource Type
- Journal article
- Publication Details
- Circulation research, Vol.88(8), pp.794-801
- Publisher
- Lippincott
- DOI
- 10.1161/hh0801.090461
- PMID
- 11325871
- ISSN
- 0009-7330
- eISSN
- 1524-4571
- Language
- English
- Date published
- 2001
- Academic Unit
- Cardiovascular Medicine; Fraternal Order of Eagles Diabetes Research Center; Biochemistry and Molecular Biology; Internal Medicine
- Record Identifier
- 9984094498002771
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