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Local recovery of Ca 2+ release in rat ventricular myocytes
Author(s) -
Sobie Eric A.,
Song LongSheng,
Lederer W. J.
Publication year - 2005
Publication title -
the journal of physiology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.802
H-Index - 240
eISSN - 1469-7793
pISSN - 0022-3751
DOI - 10.1113/jphysiol.2005.086496
Subject(s) - ryanodine receptor , biophysics , chemistry , myocyte , coupling (piping) , calcium , protein subunit , calcium signaling , medicine , receptor , biochemistry , microbiology and biotechnology , biology , materials science , organic chemistry , gene , metallurgy
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.