HYPERTENSIONAHA.116.07666.pdf
Hsiang-Ting Ho
Andriy E. Belevych
Bin Liu
Ingrid M. Bonilla
Przemyslaw b Radwanski
Igor V. Kubasov
Hector H. Valdivia
Karsten Schober
Cynthia A. Carnes
Sandor Györke
10.25376/hra.7864925.v1
https://hra.figshare.com/articles/journal_contribution/HYPERTENSIONAHA_116_07666_pdf/7864925
Although the effects and the underlying mechanism of sympathetic
stimulation on cardiac Ca handling are relatively well established both
in health and disease, the modes of action and mechanisms of
parasympathetic modulation are poorly defined. Here, we demonstrate that
parasympathetic stimulation initiates a novel mode of
excitation–contraction coupling that enhances the efficiency of cardiac
sarcoplasmic reticulum Ca store utilization. This efficient mode of
excitation–contraction coupling involves reciprocal changes in the
phosphorylation of ryanodine receptor 2 at Ser-2808 and Ser-2814.
Specifically, Ser-2808 phosphorylation was mediated by muscarinic
receptor subtype 2 and activation of PKG (protein kinase G), whereas
dephosphorylation of Ser-2814 involved activation of muscarinic receptor
subtype 3 and decreased reactive oxygen species–dependent activation of
CaMKII (Ca/calmodulin-dependent protein kinase II). The overall effect
of these changes in phosphorylation of ryanodine receptor 2 is an
increase in systolic Ca release at the low sarcoplasmic reticulum Ca
content and a paradoxical reduction in aberrant Ca leak. Accordingly,
cholinergic stimulation of cardiomyocytes isolated from failing hearts
improved Ca cycling efficiency by restoring altered ryanodine receptor 2
phosphorylation balance.
2019-03-19 19:30:49
heart failure models
calcium channels
Parasympathetic pathway
ROS level
Animal Physiology - Cell
Cardiology
Cell Biology
Physiology