Selective down-regulation of sub-endocardial ryanodine receptor expression in a rabbit model of left ventricular dysfunction

S. Currie, F.R. Quinn, R.A. Sayeed, A.M. Duncan, S. Kettlewell, G.L. Smith

Research output: Contribution to journalArticle

12 Citations (Scopus)

Abstract

Defective sarcoplasmic reticulum (SR) Ca2+ handling is evident in cardiomyopathy and may be mediated by selective dysregulation of SR Ca2+ handling proteins. To assess whether regulation of SR Ca2+ release may vary regionally within the normal and diseased heart, left ventricular transmural expression and activity of the ryanodine receptor (RyR2) was studied in a rabbit coronary artery ligation model of left ventricular dysfunction (LVD). Tissue/cells were isolated from both the sub-endocardial and subepicardial layers of the left ventricular free wall from sham-operated and coronary artery ligated rabbit hearts. Three independent methods were used to study alterations in RyR2 mRNA (real-time quantitative PCR (RT-PCR)) and protein expression (quantitative immunoblotting and [3H] ryanodine binding). These biochemical data were compared with functional measurements of fractional SR Ca2+ release from both of these regions. Data from RT-PCR revealed lower RyR2 mRNA levels in the sub-endocardium compared with subepicardium in both experimental groups with the reduction being significantly lower in the sub-endocardium from the LVD group. Quantitative analysis of RyR2 protein levels revealed the same expression patterns. Calsequestrin mRNA and protein levels showed no significant changes. This study demonstrates a lower expression level of RyR2 in the sub-endocardium of the left ventricle of rabbit hearts and is the first to show a further specific reduction in LVD. There is a corresponding decrease in fractional SR Ca2+ release in cells isolated from the sub-endocardium of hearts from the LVD group, relating these selective biochemical alterations to changes in function.

LanguageEnglish
Pages309-317
Number of pages8
JournalJournal of Molecular and Cellular Cardiology
Volume39
Issue number2
DOIs
Publication statusPublished - Aug 2005

Fingerprint

Ryanodine Receptor Calcium Release Channel
Left Ventricular Dysfunction
Sarcoplasmic Reticulum
Endocardium
Down-Regulation
Rabbits
Messenger RNA
Real-Time Polymerase Chain Reaction
Coronary Vessels
Proteins
Calsequestrin
Ryanodine
Cardiomyopathies
Immunoblotting
Heart Ventricles
Ligation
Heart Diseases

Keywords

  • ryanodine receptor
  • transmural expression
  • sarcoplasmic reticulum
  • calcium release
  • Left ventricular dysfunction

Cite this

Currie, S. ; Quinn, F.R. ; Sayeed, R.A. ; Duncan, A.M. ; Kettlewell, S. ; Smith, G.L. / Selective down-regulation of sub-endocardial ryanodine receptor expression in a rabbit model of left ventricular dysfunction. In: Journal of Molecular and Cellular Cardiology. 2005 ; Vol. 39, No. 2. pp. 309-317.
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Selective down-regulation of sub-endocardial ryanodine receptor expression in a rabbit model of left ventricular dysfunction. / Currie, S.; Quinn, F.R.; Sayeed, R.A.; Duncan, A.M.; Kettlewell, S.; Smith, G.L.

In: Journal of Molecular and Cellular Cardiology, Vol. 39, No. 2, 08.2005, p. 309-317.

Research output: Contribution to journalArticle

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T1 - Selective down-regulation of sub-endocardial ryanodine receptor expression in a rabbit model of left ventricular dysfunction

AU - Currie, S.

AU - Quinn, F.R.

AU - Sayeed, R.A.

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AU - Smith, G.L.

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