Local recovery of Ca2+ release in rat ventricular myocytes

• Published in: The Journal of physiology 2005-06, Vol.565 (2), p.441-447
• Main Authors: Sobie, Eric A., Song, Long‐Sheng, Lederer, W. J.
• Format: Article
• Language: English
• Subjects: Animals; Calcium - metabolism; Calcium Signaling - physiology; Cell Physiology; Heart Ventricles - cytology; Heart Ventricles - metabolism; Microscopy, Confocal; Myocytes, Cardiac - metabolism; Rats; Reaction Time - physiology
• ISSN: 0022-3751; 1469-7793
• DOI: 10.1113/jphysiol.2005.086496

Excitation–contraction coupling in the heart depends on the positive feedback process of Ca 2 + -induced Ca 2 + release (CICR). While CICR provides for robust triggering of Ca 2 + sparks, the mechanisms underlying their termination remain unknown. At present, it is unclear how a cluster of Ca 2 + release channels (ryanodine receptors or RyRs) can be made to turn off when their activity is sustained by the Ca 2 + release itself. We use a novel experimental approach to investigate indirectly this issue by exploring restitution of Ca 2 + 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 Ca 2 + spark sites. Examination of these repetitive Ca 2 + 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 ∼80 ms. We conclude that restitution of Ca 2 + 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 Ca 2 + to SR regulatory proteins.