Global, synchronous oscillations in cytosolic calcium and adherence in bradykinin-stimulated Madin-Darby canine kidney cells.
OBJECTIVE
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 18alpha-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.


CONCLUSIONS
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.
De Blasio
B F
BF
The Niels Bohr Institute, University of Copenhagen, Copenhagen, Denmark.
Røttingen
J-A
JA
Sand
K L
KL
Giaever
I
I
Iversen
J-G
JG
D000818:Animals; D001920:Bradykinin / Q000494:pharmacology*; D002118:Calcium / Q000378:metabolism*; D020013:Calcium Signaling / Q000502:physiology; D002448:Cell Adhesion / Q000502:physiology*; D002460:Cell Line; D002462:Cell Membrane / Q000502:physiology; D003600:Cytosol / Q000378:metabolism*; D004285:Dogs; D017097:Electric Impedance; D017629:Gap Junctions / Q000187:drug effects; D006034:Glycyrrhetinic Acid / Q000031:analogs & derivatives / Q000494:pharmacology; D007668:Kidney / Q000166:cytology; D015398:Signal Transduction / Q000502:physiology
C119129:18alpha-glycyrrhetinic acid; D006034:Glycyrrhetinic Acid; D001920:Bradykinin; D002118:Calcium