Global, synchronous oscillations in cytosolic calcium and adherence in bradykinin-stimulated Madin-Darby canine kidney cells

Authors

  • B. F. De Blasio,

    1.  The Niels Bohr Institute, University of Copenhagen, Copenhagen, Denmark
    2.  Department of Physics, University of Oslo, Oslo, Norway
    3.  Laboratory for Intracellular Signalling, Department of Physiology, University of Oslo, Oslo, Norway
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  • J.-A. Røttingen,

    1.  Laboratory for Intracellular Signalling, Department of Physiology, University of Oslo, Oslo, Norway
    2.  Institute for Nutrition Research, University of Oslo, Oslo, Norway
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  • K. L. Sand,

    1.  Laboratory for Intracellular Signalling, Department of Physiology, University of Oslo, Oslo, Norway
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  • I. Giaever,

    1.  Department of Physics, University of Oslo, Oslo, Norway
    2.  Rensselaer Polytechnic Institute, Troy, NY, USA
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  • J.-G. Iversen

    1.  Laboratory for Intracellular Signalling, Department of Physiology, University of Oslo, Oslo, Norway
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Professor J.-G. Iversen, Department of Physiology, University of Oslo, PO Box 1103, Blindern, N-0317 Oslo, Norway.

Abstract

Aims and Methods:  Intercellular Ca2+ oscillations are a universal mode of signalling in both excitable and non-excitable cells. Here, we study the relationship between Ca2+ signalling and coherent changes in adhesion properties by measuring the transepithelial impedance across bradykinin-stimulated Madin-Darby canine kidney (MDCK) cell layers grown on a microelectrode. During hormone stimulation, the impedance is found to oscillate, reflecting that the cells undergo morphological/adhesive alterations with high spatio-temporal organization. The experiments are supplemented with parallel, digital imaging fluorescence microscopy of bradykinin-induced single-cell Ca2+ oscillations.

Results:  In agreement with previous experiments, MDCK cells are found to elicit synchronous, multicellular Ca2+ oscillations in response to hormone stimulus. The periods of the Ca2+ oscillations and the electrical fluctuations are found to coincide. Further, blocking of gap junctions by 18α-glycyrrhetinic acid causes a loss of synchrony in Ca2+ signals and inhibition of impedance oscillations, emphasizing the importance of gap junctions in the signal transduction process.

Conclusion:  Based on these observations it is concluded that the co-ordinated adhesive changes in MDCK cells are a direct consequence of synchronized Ca2+ oscillations.

Calcium signalling represents an efficient way of organizing physiological responses in a tissue. A possible functional implication of the structural changes might be to modulate transportation of various substances across the cell sheet.

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