期刊
PFLUGERS ARCHIV-EUROPEAN JOURNAL OF PHYSIOLOGY
卷 465, 期 12, 页码 1775-1784出版社
SPRINGER
DOI: 10.1007/s00424-013-1312-2
关键词
Zebrafish; Sarcoplasmic reticulum; Ca2+-induced Ca2+ release; Ryanodine receptor; Phosphorylation; Heart
类别
资金
- National Institutes of Health [HL62426, HL75494]
- Research Career Development Award from The Schweppe Foundation
- American Heart Association Fellowship [14510047]
The zebrafish serves as a promising transgenic animal model that can be used to study cardiac Ca2+ regulation. However, mechanisms of sarcoplasmic reticulum (SR) Ca2+ handling in the zebrafish heart have not been systematically explored. We found that in zebrafish ventricular myocytes, the action potential-induced Ca2+ transient is mainly (80 %) mediated by Ca2+ influx via L-type Ca2+ channels (LTCC) and only 20 % by Ca2+ released from the SR. This small contribution of the SR to the Ca2+ transient was not the result of depleted SR Ca2+ load. We found that the ryanodine receptor (RyR) expression level in zebrafish myocytes was similar to 72 % lower compared to rabbit myocytes. In permeabilized myocytes, increasing cytosolic [Ca2+] from 100 to 350 nM did not trigger SR Ca2+ release. However, an application of a low dose of caffeine activated Ca2+ sparks. These results show that the zebrafish cardiac RyR has low sensitivity to the mechanism of Ca2+-induced Ca2+ release. Activation of protein kinase A by forskolin increased phosphorylation of the RyR in zebrafish myocardium. In half of the studied cells, an increased Ca2+ transient by forskolin was entirely mediated by augmentation of LTCC current. In the remaining myocytes, the forskolin action was associated with an increase of both LTCC and SR Ca2+ release. These results indicate that the mechanism of excitation-contraction coupling in zebrafish myocytes differs from the mammalian one mainly because of the small contribution of SR Ca2+ release to the Ca2+ transient. This difference is due to a low sensitivity of RyRs to cytosolic [Ca2+].
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