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Paradoxical SR Ca 2+ release in guinea‐pig cardiac myocytes after β‐adrenergic stimulation revealed by two‐photon photolysis of caged Ca 2+
Author(s) -
Lindegger Nicolas,
Niggli Ernst
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.2005.084376
Subject(s) - ryanodine receptor , stimulation , myocyte , chemistry , endoplasmic reticulum , medicine , biophysics , endocrinology , biology , biochemistry
In heart muscle the amplification and shaping of Ca 2+ signals governing contraction are orchestrated by recruiting a variable number of Ca 2+ sparks. Sparks reflect Ca 2+ release from the sarcoplasmic reticulum (SR) via Ca 2+ release channels (ryanodine receptors, RyRs). RyRs are activated by Ca 2+ influx via L‐type Ca 2+ channels with a specific probability that may depend on regulatory mechanisms (e.g. β‐adrenergic stimulation) or diseased states (e.g. heart failure). Changes of RyR phosphorylation may be critical for both regulation and impaired function in disease. Using UV flash photolysis of caged Ca 2+ and short applications of caffeine in guinea‐pig ventricular myocytes, we found that Ca 2+ release signals on the cellular level were largely governed by global SR content. During β‐adrenergic stimulation resting myocytes exhibited smaller SR Ca 2+ release signals when activated by photolysis (62.3% of control), resulting from reduced SR Ca 2+ content under these conditions (58.6% of control). In contrast, local signals triggered with diffraction limited two‐photon photolysis displayed the opposite behaviour, exhibiting a larger Ca 2+ release (164% of control) despite reduced global and local SR Ca 2+ content. This apparent paradox implies changes of RyR open probabilities after β‐adrenergic stimulation, enhancing local regenerativity and reliability of Ca 2+ signalling. Thus, our results underscore the importance of phosphorylation of RyRs (or of a related protein), as a regulatory physiological mechanism that may also provide new therapeutic avenues to recover impaired Ca 2+ signalling during cardiac disease.