Related Experiment Videos
Unaltered ryanodine receptor protein levels in ischemic cardiomyopathy
W Schillinger1, M Meyer, G Kuwajima
1Medizinische Klinik III, Universität Freiburg, Germany.
Insights
In ischemic cardiomyopathy, sarcoplasmic reticulum calcium uptake proteins decrease, while release channels remain stable. These findings mirror changes seen in dilated cardiomyopathy, suggesting similar SR protein alterations in heart failure.
Area of Science:
- Cardiology
- Molecular Biology
- Biochemistry
Background:
- Previous studies show unchanged ryanodine receptor protein in dilated cardiomyopathy.
- Ryanodine receptor mRNA decreases in ischemic cardiomyopathy, but protein levels are unknown.
Purpose of the Study:
- To investigate protein levels of key sarcoplasmic reticulum (SR) proteins in ischemic cardiomyopathy.
- Compare SR protein alterations in ischemic versus dilated cardiomyopathy.
Main Methods:
- Western blot analysis was used to quantify protein levels.
- Measurements were performed on human myocardium from nonfailing and end-stage failing hearts (ischemic cardiomyopathy).
- Proteins analyzed included ryanodine receptor, calsequestrin, and SR-Ca(2+)-ATPase.
Main Results:
- Calsequestrin protein levels were similar between nonfailing and failing hearts.
- Ryanodine receptor protein levels remained unchanged in ischemic cardiomyopathy.
- SR-Ca(2+)-ATPase protein levels were significantly decreased (31-30%) in failing hearts.
Conclusions:
- Ischemic cardiomyopathy shows reduced SR calcium uptake relative to release sites.
- SR protein alterations in ischemic cardiomyopathy are comparable to those in dilated cardiomyopathy.
Abstract:
Previous studies on sarcoplasmic reticulum calcium release channel (ryanodine receptor) demonstrated that protein levels are unchanged in myocardium from hearts with end-stage failing dilated cardiomyopathy. In ischemic cardiomyopathy, ryanodine receptor mRNA levels were shown to be decreased but no data on protein levels are available. Accordingly, protein levels of ryanodine receptor, calsequestrin, and sarcoplasmic reticulum calcium-ATPase (SR-Ca(2+)-ATPase) were measured by Western blot analysis in nonfailing human myocardium (n = 7) and in end-stage failing myocardium due to ischemic cardiomyopathy (n = 14). Protein levels of calsequestrin which is the major sarcoplasmic reticulum calcium storage protein were similar in nonfailing myocardium and in myocardium from end-stage failing hearts with ischemic cardiomyopathy. Ryanodine receptor protein levels, normalized to total protein or calsequestrin were also unchanged in ischemic cardiomyopathy. In contrast, protein levels of SR-Ca(2+)-ATPase normalized to total protein or calsequestrin were decreased by 31 and 30%, respectively (p < 0.05). The data indicate that (1) sarcoplasmic reticulum calcium uptake sites are decreased relative to the release sites in ischemic cardiomyopathy, and (2) alterations of sarcoplasmic proteins are similar in ischemic and dilated cardiomyopathy.