β-adrenergic stimulation synchronizes intracellular Ca 2+ release during excitation-contraction coupling in cardiac myocytes

Long Sheng Song, Shi Qiang Wang, Rui Ping Xiao, Harold Spurgeon, Edward Lakatta, Heping Cheng

Research output: Contribution to journalArticle

Abstract

To elucidate microscopic mechanisms underlying the modulation of cardiac excitation-contraction (EC) coupling by β-adrenergic receptor (β-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. β-AR stimulation by norepinephrine plus an α 1-adrenergic blocker, prazosin, increased the amplitude of SR Ca 2+ release flux (J SR), its running integral (∫J SR), and L-type Ca 2+ channel current (I Ca, and it shifted their bell-shaped voltage dependence leftward by ≈ 10 mV, with the relative effects ranking I Ca> J SR>∫J 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. β-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, β-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 β-AR modulation of cardiac inotropy.

Original languageEnglish (US)
Pages (from-to)794-801
Number of pages8
JournalCirculation Research
Volume88
Issue number8
StatePublished - Apr 27 2001
Externally publishedYes

Fingerprint

Excitation Contraction Coupling
Sarcoplasmic Reticulum
Cardiac Myocytes
Adrenergic Agents
Myofibrils
Adrenergic Antagonists
Prazosin
Confocal Microscopy
Adrenergic Receptors
Norepinephrine

Keywords

  • β-adrenergic receptor
  • Excitation-contraction coupling
  • Heart cells
  • L-type Ca channel current
  • Ryanodine receptors

ASJC Scopus subject areas

  • Physiology
  • Cardiology and Cardiovascular Medicine

Cite this

β-adrenergic stimulation synchronizes intracellular Ca 2+ release during excitation-contraction coupling in cardiac myocytes. / Song, Long Sheng; Wang, Shi Qiang; Xiao, Rui Ping; Spurgeon, Harold; Lakatta, Edward; Cheng, Heping.

In: Circulation Research, Vol. 88, No. 8, 27.04.2001, p. 794-801.

Research output: Contribution to journalArticle

Song, Long Sheng ; Wang, Shi Qiang ; Xiao, Rui Ping ; Spurgeon, Harold ; Lakatta, Edward ; Cheng, Heping. / β-adrenergic stimulation synchronizes intracellular Ca 2+ release during excitation-contraction coupling in cardiac myocytes. In: Circulation Research. 2001 ; Vol. 88, No. 8. pp. 794-801.
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AU - Song, Long Sheng

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AU - Spurgeon, Harold

AU - Lakatta, Edward

AU - Cheng, Heping

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N2 - To elucidate microscopic mechanisms underlying the modulation of cardiac excitation-contraction (EC) coupling by β-adrenergic receptor (β-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. β-AR stimulation by norepinephrine plus an α 1-adrenergic blocker, prazosin, increased the amplitude of SR Ca 2+ release flux (J SR), its running integral (∫J SR), and L-type Ca 2+ channel current (I Ca, and it shifted their bell-shaped voltage dependence leftward by ≈ 10 mV, with the relative effects ranking I Ca> J SR>∫J 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. β-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, β-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 β-AR modulation of cardiac inotropy.

AB - To elucidate microscopic mechanisms underlying the modulation of cardiac excitation-contraction (EC) coupling by β-adrenergic receptor (β-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. β-AR stimulation by norepinephrine plus an α 1-adrenergic blocker, prazosin, increased the amplitude of SR Ca 2+ release flux (J SR), its running integral (∫J SR), and L-type Ca 2+ channel current (I Ca, and it shifted their bell-shaped voltage dependence leftward by ≈ 10 mV, with the relative effects ranking I Ca> J SR>∫J 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. β-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, β-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 β-AR modulation of cardiac inotropy.

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KW - L-type Ca channel current

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