Local recovery of Ca2+ release in rat ventricular myocytes

Eric A Sobie; Long-Sheng Song; W J Lederer

doi:10.1113/jphysiol.2005.086496

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Local recovery of Ca2+ release in rat ventricular myocytes

Journal article

Open access

Peer reviewed

Local recovery of Ca2+ release in rat ventricular myocytes

Eric A Sobie, Long-Sheng Song and W J Lederer

The Journal of physiology, Vol.565(Pt 2), pp.441-447

06/01/2005

DOI: 10.1113/jphysiol.2005.086496

PMCID: PMC1464523

PMID: 15817631

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https://doi.org/10.1113/jphysiol.2005.086496View

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Abstract

Excitation-contraction coupling in the heart depends on the positive feedback process of Ca2+-induced Ca2+ release (CICR). While CICR provides for robust triggering of Ca2+ sparks, the mechanisms underlying their termination remain unknown. At present, it is unclear how a cluster of Ca2+ release channels (ryanodine receptors or RyRs) can be made to turn off when their activity is sustained by the Ca2+ release itself. We use a novel experimental approach to investigate indirectly this issue by exploring restitution of Ca2+ sparks. We exploit the fact that ryanodine can bind, nearly irreversibly, to an RyR subunit (monomer) and increase the open probability of the homotetrameric channel. By applying low concentrations of ryanodine to rat ventricular myocytes, we observe repeated activations of individual Ca2+ spark sites. Examination of these repetitive Ca2+ sparks reveals that spark amplitude recovers with a time constant of 91 ms whereas the sigmoidal recovery of triggering probability lags behind amplitude recovery by approximately 80 ms. We conclude that restitution of Ca2+ sparks depends on local refilling of SR stores after depletion and may also depend on another time-dependent process such as recovery from inactivation or a slow conformational change after rebinding of Ca2+ to SR regulatory proteins.

Microscopy, Confocal

Heart Ventricles - cytology

Animals

Calcium - metabolism

Calcium Signaling - physiology

Myocytes, Cardiac - metabolism

Rats

Heart Ventricles - metabolism

Reaction Time - physiology

Details

Title: Subtitle: Local recovery of Ca2+ release in rat ventricular myocytes
Creators: Eric A Sobie - Medical Biotechnology Center, 725 W. Lombard Street, Baltimore, MD 21201, USA
Long-Sheng Song
W J Lederer
Resource Type: Journal article
Publication Details: The Journal of physiology, Vol.565(Pt 2), pp.441-447
DOI: 10.1113/jphysiol.2005.086496
PMID: 15817631
PMCID: PMC1464523
ISSN: 0022-3751
eISSN: 1469-7793
Grant note: R01 HL076230-01A1 / NHLBI NIH HHS R01 HL076230 / NHLBI NIH HHS
Language: English
Date published: 06/01/2005
Academic Unit: Cardiovascular Medicine; Fraternal Order of Eagles Diabetes Research Center; Biochemistry and Molecular Biology; Internal Medicine
Record Identifier: 9984094731002771

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