Thermodynamically Irreversible Gating of Ryanodine Receptors in Situ Revealed by Stereotyped Duration of Release in Ca2+ Sparks

Shi-Qiang Wang; Long-Sheng Song; Le Xu; Gerhard Meissner; Edward G Lakatta; Eduardo Ríos; Michael D Stern; Heping Cheng

doi:10.1016/S0006-3495(02)75165-5

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Thermodynamically Irreversible Gating of Ryanodine Receptors in Situ Revealed by Stereotyped Duration of Release in Ca2+ Sparks

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Thermodynamically Irreversible Gating of Ryanodine Receptors in Situ Revealed by Stereotyped Duration of Release in Ca2+ Sparks

Shi-Qiang Wang, Long-Sheng Song, Le Xu, Gerhard Meissner, Edward G Lakatta, Eduardo Ríos, Michael D Stern and Heping Cheng

Biophysical journal, Vol.83(1), pp.242-251

07/2002

DOI: 10.1016/S0006-3495(02)75165-5

PMCID: PMC1302143

PMID: 12080116

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Abstract

For a single or a group of Markov channels gating reversibly, distributions of open and closed times should be the sum of positively weighted decaying exponentials. Violation of this microscopic reversibility has been demonstrated previously on a number of occasions at the single channel level, and has been attributed to possible channel coupling to external sources of free energy. Here we show that distribution of durations of Ca2+ release underlying Ca2+ sparks in intact cardiac myocytes exhibits a prominent mode at ∼8ms. Analysis of the cycle time for repetitive sparks at hyperactive sites revealed no intervals briefer than ∼35ms and a mode at ∼90ms. These results indicate that, regardless of whether Ca2+ sparks are single-channel or multi-channel in origin, they are generated by thermodynamically irreversible stochastic processes. In contrast, data from planar lipid bilayer experiments were consistent with reversible gating of RyR under asymmetric cis (4μM) and trans Ca2+ (10mM), suggesting that the irreversibility for Ca2+ spark genesis may reside at a supramolecular level. Modeling suggests that Ca2+-induced Ca2+ release among adjacent RyRs may couple the external energy derived from Ca2+ gradients across the SR to RyR gating in situ, and drive the irreversible generation of Ca2+ sparks.

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Title: Subtitle: Thermodynamically Irreversible Gating of Ryanodine Receptors in Situ Revealed by Stereotyped Duration of Release in Ca2+ Sparks
Creators: Shi-Qiang Wang - Laboratory of Cardiovascular Sciences, National Institute on Aging, National Institutes of Health, Baltimore, Maryland 21224
Long-Sheng Song - Laboratory of Cardiovascular Sciences, National Institute on Aging, National Institutes of Health, Baltimore, Maryland 21224
Le Xu - Department of Biochemistry and Biophysics, University of North Carolina, Chapel Hill, North Carolina 27599
Gerhard Meissner - Department of Biochemistry and Biophysics, University of North Carolina, Chapel Hill, North Carolina 27599
Edward G Lakatta - Laboratory of Cardiovascular Sciences, National Institute on Aging, National Institutes of Health, Baltimore, Maryland 21224
Eduardo Ríos - Department of Molecular Biophysics and Physiology, Rush University, Chicago, Illinois 60612 USA
Michael D Stern - Laboratory of Cardiovascular Sciences, National Institute on Aging, National Institutes of Health, Baltimore, Maryland 21224
Heping Cheng - Laboratory of Cardiovascular Sciences, National Institute on Aging, National Institutes of Health, Baltimore, Maryland 21224
Resource Type: Journal article
Publication Details: Biophysical journal, Vol.83(1), pp.242-251
Publisher: Elsevier Inc
DOI: 10.1016/S0006-3495(02)75165-5
PMID: 12080116
PMCID: PMC1302143
ISSN: 0006-3495
eISSN: 1542-0086
Language: English
Date published: 07/2002
Academic Unit: Cardiovascular Medicine; Fraternal Order of Eagles Diabetes Research Center; Biochemistry and Molecular Biology; Internal Medicine
Record Identifier: 9984094729402771

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