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Increased Ca2+ sensitivity and protein expression of SERCA 2a in situations of chronic β3-adrenoceptor deficiency

  • Cardiovascular System
  • Published:
Pflügers Archiv - European Journal of Physiology Aims and scope Submit manuscript

Abstract

This study investigated the influence of chronic β3-adrenoceptor deficiency on myocardial function. Therefore, we investigated Ca2+-regulatory proteins, SERCA 2a activity, and myofibrillar and mitochondrial function in hearts of wild-type (WT, n=7) and β3-adrenoceptor knockout mice (β3-KNO, n=7). Morphometric heart analysis showed no difference between WT and β3-KNO. No alterations were observed for the protein expression of the ryanodine receptor or phospholamban. However, in β3-KNO mice, protein expression of SERCA 2a and phospholamban phosphorylation were significantly increased. These changes were accompanied by an increased SERCA 2a activity in β3-KNO. Alterations in phospholamban phosphorylation were independent of alterations in β1/β2-adrenoceptor distribution and protein expression of G proteins in β3-KNO. Measurement of myofibrillar Ca2+ sensitivity showed no difference in the Ca2+/force relation for WT and β3-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 β3-KNO. The conclusion is that depression of β3-adrenergic stimulation may modulate the protein expression of SERCA 2a and phospholamban phosphorylation, thereby improving sarcoplasmic reticulum Ca2+ uptake. Thus, β3-adrenergic depression may be a therapeutic aim in situations of impaired SERCA 2a activity, e.g. for the treatment of heart failure.

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Acknowledgements

This study was supported by the Center for Molecular Medicine Cologne (CMMC, R.W.), University of Cologne. This publication contains data from the doctoral thesis of C.Z. We would like to thank Mrs. Esra Koeroglu, Mrs. Kerstin Schenk, Mrs. Nadine Lottmann and Mrs. Katja Roesler for their technical support.

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Authors and Affiliations

  1. Laboratory of Muscle Research and Molecular Cardiology, Department of Internal Medicine III, University of Cologne, Cologne, Germany

    Christoph Ziskoven, Sabrina Grafweg, Birgit Bölck, Robert H. G. Schwinger & Klara Brixius

  2. Institute of Vegetative Physiology, University of Cologne, Cologne, Germany

    Rudolf J. Wiesner

  3. Center for Molecular Medicine Cologne (CMMC), University of Cologne, Cologne, Germany

    Rudolf J. Wiesner

  4. Département de Biochimie Médicale, Centre Médical Universitaire, Université de Genève, Geneva, Switzerland

    Maria Jimenez & Jean-Paul Giacobino

  5. Department of Molecular and Cellular Sport Medicine, Institute of Cardiology and Sport Medicine, German Sport University, Carl-Diem-Weg 6, 50933, Cologne, Germany

    W. Bloch & Klara Brixius

  6. Medizinische Klinik II, Klinikum Weiden, Weiden i. d. OPf., Weiden, Germany

    Robert H. G. Schwinger

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  1. Christoph Ziskoven
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  2. Sabrina Grafweg
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Correspondence to Klara Brixius.

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Ziskoven, C., Grafweg, S., Bölck, B. et al. Increased Ca2+ sensitivity and protein expression of SERCA 2a in situations of chronic β3-adrenoceptor deficiency. Pflugers Arch - Eur J Physiol 453, 443–453 (2007). https://doi.org/10.1007/s00424-006-0137-7

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