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

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 Ca 2+ 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.