Increased Ca2+ sensitivity and protein expression of SERCA 2a in situations of chronic beta3-adrenoceptor deficiency

Christoph Ziskoven, Sabrina Grafweg, Birgit Bölck, Rudolf J Wiesner, Maria Jimenez, Jean-Paul Giacobino, W Bloch, Robert H G Schwinger, Klara Brixius

Publication: Contribution to journalJournal articlesResearchpeer-review

Abstract

This study investigated the influence of chronic beta(3)-adrenoceptor deficiency on myocardial function. Therefore, we investigated Ca(2+)-regulatory proteins, SERCA 2a activity, and myofibrillar and mitochondrial function in hearts of wild-type (WT, n=7) and beta(3)-adrenoceptor knockout mice (beta(3)-KNO, n=7). Morphometric heart analysis showed no difference between WT and beta(3)-KNO. No alterations were observed for the protein expression of the ryanodine receptor or phospholamban. However, in beta(3)-KNO mice, protein expression of SERCA 2a and phospholamban phosphorylation were significantly increased. These changes were accompanied by an increased SERCA 2a activity in beta(3)-KNO. Alterations in phospholamban phosphorylation were independent of alterations in beta(1)/beta(2)-adrenoceptor distribution and protein expression of G proteins in beta(3)-KNO. Measurement of myofibrillar Ca(2+) sensitivity showed no difference in the Ca(2+)/force relation for WT and beta(3)-KNO. The same seems to hold true for mitochondrial function since the protein expressions of cytochrome c, uncoupling protein 3 and cytochrome c oxidase subunit IV were similar in WT and beta(3)-KNO. The conclusion is that depression of beta(3)-adrenergic stimulation may modulate the protein expression of SERCA 2a and phospholamban phosphorylation, thereby improving sarcoplasmic reticulum Ca(2+) uptake. Thus, beta(3)-adrenergic depression may be a therapeutic aim in situations of impaired SERCA 2a activity, e.g. for the treatment of heart failure.

Original languageEnglish
JournalPflügers Archiv : European journal of physiology
Volume453
Issue number4
Pages (from-to)443-53
Number of pages11
ISSN0031-6768
DOIs
Publication statusPublished - 01.01.2007

Research areas and keywords

  • Animals
  • Calcium
  • Calcium-Binding Proteins
  • Echocardiography
  • GTP-Binding Proteins
  • Gene Expression
  • Heart Failure
  • Immunoblotting
  • Male
  • Mice
  • Mice, Knockout
  • Mitochondrial Proteins
  • Myofibrils
  • Phosphorylation
  • Receptors, Adrenergic, beta-3
  • Ryanodine Receptor Calcium Release Channel
  • Sarcoplasmic Reticulum
  • Sarcoplasmic Reticulum Calcium-Transporting ATPases
  • Signal Transduction

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