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Ryanodine receptor type-1 (RyR1) expression and protein S-nitrosylation pattern in human soleus myofibres following bed rest and exercise countermeasure

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Abstract

The ryanodine receptor type-I (RyR1) is one key player of the excitation–contraction coupling (E-CC) machinery. However, RyR1 expression in human skeletal muscle disuse and plasticity changes are not well documented. We studied the expression and the functional modifications of RyR1 following prolonged bed rest (BR) without and with exercise countermeasure (Resistive Vibration Exercise, RVE). Soleus biopsies were taken from a non-trained control (BR-CTRL) and trained (BR-RVE) group (each n = 10) before and after BR. In BR-CTRL group, a fibre type-specific immunopattern of RyR1 (type-I < type-II) was documented, and RyR1 immunofluorescence intensity and protein expression together with [3H]ryanodine binding were decreased after BR. In BR-RVE group, RyR1 immunosignals were increased and fiber type specificity was no longer present. RyR1 protein expression was unchanged, whereas [3H]ryanodine binding increased after BR. Confocal and biochemical analysis confirmed subcellular co-localisation and protein–protein interaction of RyR1 with nitric oxide (NO)-synthase type-1 (NOS1). S-nitrosylation of RyR1 was increased in BR-CTRLpost only, suggesting a reduction of RyR1 open channel probability by nitrosylation mechanisms following prolonged disuse. We conclude that following extended body deconditioning in bed rest, RVE countermeasure maintained normal RyR1 expression and nitrosylation patterns required for adequate E-CC in human performance control.

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Acknowledgments

We are indebted to Dr. Benedikt G.H. Schoser (LMU Munich, Germany) for providing additional human muscle biopsies and Dr. John Mackrill (UCC Cork, Ireland) for providing the GST-FKBP12 construct. This study was supported by grants from the European Space Agency (ESA), Grant No. 14431/02/NL/SH2), and the German AeroSpace (DLR), Grant No. 50WB0145 (to D.B.). Many thanks to the staff of the Centre for Muscle & Bone Research at CBF, and all participants of the Berlin Bed Rest Study 2003 and 2004. Thanks to Leica Microsystems (http://www.leica-microsystems.com) for technical support.

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Authors and Affiliations

  1. Center of Space Medicine Berlin, Neuromuscular Group, Charité, Universitätsmedizin Berlin, Campus Benjamin Franklin, Arnimallee 22, 14195, Berlin, Germany

    Michele Salanova, Gudrun Schiffl & Dieter Blottner

  2. Department of Vegetative Anatomy, Charité, Universitätsmedizin Berlin, CBF, Arnimallee 22, 14195, Berlin, Germany

    Michele Salanova & Dieter Blottner

  3. Institute for Biophysical and Clinical Research into Human Movement, Manchester Metropolitan University, Hassal Rd., Alsager, ST7 2QL, UK

    Jörn Rittweger

  4. Center for Muscle and Bone Research, Charité, Universitätsmedizin Berlin, Campus Benjamin Franklin, Hindenburgdamm 30, 12200, Berlin, Germany

    Dieter Felsenberg

  5. Center of Space Medicine, Department of Vegetative Anatomy, Charité, Universitätsmedizin Berlin, Campus Benjamin Franklin, Arnimallee 22, 14195, Berlin, Germany

    Michele Salanova

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  1. Michele Salanova
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  2. Gudrun Schiffl
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Correspondence to Michele Salanova.

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Salanova, M., Schiffl, G., Rittweger, J. et al. Ryanodine receptor type-1 (RyR1) expression and protein S-nitrosylation pattern in human soleus myofibres following bed rest and exercise countermeasure. Histochem Cell Biol 130, 105–118 (2008). https://doi.org/10.1007/s00418-008-0399-6

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