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Acetylcholine-induced Ca2+ oscillations are modulated by a Ca2+ regulation of InsP3R2 in rat portal vein myocytes

  • Cell and Molecular Physiology
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Abstract

Oscillations of cytosolic Ca2+ levels are believed to have important roles in various metabolic and signalling processes in many cell types. Previously, we have demonstrated that acetylcholine (ACh) evokes Ca2+ oscillations in vascular myocytes expressing InsP3R1 and InsP3R2, whereas transient responses are activated in vascular myocytes expressing InsP3R1 alone. The molecular mechanisms underlying oscillations remain to be described in these native smooth muscle cells. Two major hypotheses are proposed to explain this crucial signalling activity: (1) Ca2+ oscillations are activated by InsP3 oscillations; and (2) Ca2+ oscillations depend on the regulation of the InsP3R by both InsP3 and Ca2+. In the present study, we used a fluorescent InsP3 biosensor and revealed that ACh induced a transient InsP3 production in all myocytes. Moreover, steady concentrations of 3F-InsP3, a poorly hydrolysable analogue of InsP3, and pharmacological activation of PLC evoked Ca2+ oscillations. Increasing cytosolic Ca2+ inhibited the ACh-induced calcium oscillations but not the transient responses and strongly reduced the 3F-InsP3-evoked Ca2+ response in oscillating cells but not in non-oscillating cells. These results suggest that, in native vascular myocytes, ACh-induced InsP3 production is transient and Ca2+ oscillations depend on a Ca2+ modulation of InsP3R2.

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Acknowledgements

We acknowledge T. Meyer for giving us the EGFP-PH-PLC construct encoding InsP3 biosensor. This work was supported by grants from Centre National de la Recherche Scientifique (CNRS), Centre National des Etudes Spatiales (CNES) and Association Française contre les myopathies (AFM), France. JL Morel thanks Dr A. Prévot for proofreading. This work is dedicated to Jean-Louis Lavie.

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Authors and Affiliations

  1. Molecular Neurobiology, Medical Biochemistry and Biophysics, Karolinska Institutet, Scheeles väg 2, 171 77, Stockholm, Sweden

    Nicolas Fritz

  2. CNRS UMR 5017, Université Bordeaux2, 33076, Bordeaux, France

    Jean Mironneau

  3. Centre de Neurosciences Intégratives et Cognitives, Université Bordeaux, Bordeaux, France

    Nathalie Macrez & Jean-Luc Morel

  4. CNRS, UMR 5228, CNIC, Talence, France

    Nathalie Macrez & Jean-Luc Morel

  5. Centre de Neurosciences Intégratives et Cognitives, CNRS UMR 5228, Universités de Bordeaux, avenue des facultés, 33405, Talence, France

    Jean-Luc Morel

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  1. Nicolas Fritz
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  2. Jean Mironneau
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  3. Nathalie Macrez
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  4. Jean-Luc Morel
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Correspondence to Jean-Luc Morel.

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Fritz, N., Mironneau, J., Macrez, N. et al. Acetylcholine-induced Ca2+ oscillations are modulated by a Ca2+ regulation of InsP3R2 in rat portal vein myocytes. Pflugers Arch - Eur J Physiol 456, 277–283 (2008). https://doi.org/10.1007/s00424-007-0379-z

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  • DOI: https://doi.org/10.1007/s00424-007-0379-z

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