Spontaneous diastolic contractions and phosphorylation of the cardiac ryanodine receptor at serine-2808 in congestive heart failure in rat

The role of phosphorylation of the ryanodine receptor at serine-2808 (RyRS2808) in congestive heart failure (CHF) is controversial, and effects of RyRS2808 phosphorylation on contraction are unclear. It has been reported that diastolic sarcomere length (SL) fluctuations accompany propagating contrac...

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Bibliographic Details
Published in:Cardiovascular research 2006, Vol.69 (1), p.140-151
Main Authors: OBAYASHI, Masakazu, BAILONG XIAO, STUYVERS, Bruno D, DAVIDOFF, Allen W, JIE MEI, CHEN, S. R, TER KEURS, Henk E. D. J
Format: Article
Language:English
Subjects:
Adrenergic beta-Agonists - pharmacology
Adrenergic beta-Antagonists - pharmacology
Animals
Biological and medical sciences
Cardiology. Vascular system
Coronary heart disease
Diastole
Echocardiography
Heart
Heart Failure - metabolism
Heart Failure - physiopathology
Heart failure, cardiogenic pulmonary edema, cardiac enlargement
Isoproterenol - pharmacology
Male
Medical sciences
Metoprolol - pharmacology
Models, Animal
Myocardial Contraction
Phosphorylation
Rats
Rats, Inbred BN
Ryanodine Receptor Calcium Release Channel - metabolism
Sarcoplasmic Reticulum - drug effects
Sarcoplasmic Reticulum - metabolism
Serine - metabolism
Tacrolimus - pharmacology
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Summary:The role of phosphorylation of the ryanodine receptor at serine-2808 (RyRS2808) in congestive heart failure (CHF) is controversial, and effects of RyRS2808 phosphorylation on contraction are unclear. It has been reported that diastolic sarcomere length (SL) fluctuations accompany propagating contractile waves due to propagating SR Ca2+ release in trabeculae from rats with CHF. Here, we studied the influence of RyR destabilization by FK506 and isoproterenol on twitch force (Ftw) and SL fluctuations in right ventricular (RV) trabeculae. We measured phosphorylation of RyRS2808 in rats with myocardial infarction (MI) with or without beta-blockade and in rats during isoproterenol stimulation in order to assess the role of RyRS2808 phosphorylation in SL fluctuations in failing hearts. Five groups of male Lewis Brown-Norway rats were studied 3 months after MI: i) Sham; ii) MI with CHF (cMI); iii) MI without CHF; iv) metoprolol-treated MI, with and without CHF. The root mean square (RMSSL) of SL fluctuations in RV trabeculae was calculated. RMSSL increased strongly both following a short train of stimuli at 2.5 Hz and following catecholamine activation in trabeculae from MI with CHF, resulting in a decrease in Ftw in proportion to RMSSL. RyRS2808 phosphorylation was increased significantly in the left ventricle (LV; approximately 58%, P
ISSN:0008-6363
1755-3245
DOI:10.1016/j.cardiores.2005.07.010