Nontransformed cells can normalize gap junctional communication with transformed cells.
We demonstrate that the Src kinase can augment gap junctional communication between cells derived from homozygous null Cx43 knockout mice. The total conductance between Src transformed cells was nearly twice that of nontransformed cells. In addition, the unitary conductance of the majority of single channel events between transformed cells was about 35% greater than that of nontransformed cells. Analysis showed that both nontransformed and transformed cells expressed at least two populations of channels, suggesting that Src increased junctional conductance by up-regulating one population and/or by increasing the unitary conductance of another population of channels. Interestingly, the conductance displayed by heterologous pairs of transformed and nontransformed cells resembled that of nontransformed cells. The majority of single channel events between heterologous pairs shifted back to lower conductances that were exhibited by nontransformed cells. Thus, nontransformed cells can effectively "normalize" the conductance of gap junction channels expressed by adjacent tumor cells.
Valiunas
Virginijus
V
Department of Physiology and Biophysics, School of Medicine, Basic Science Tower L6, Health Science Complex, State University of New York at Stony Brook, 11794-8661, USA. vvaliunas@notes.cc.sunysb.edu
Bechberger
John F
JF
Naus
Christian C G
CC
Brink
Peter R
PR
Goldberg
Gary S
GS
D000818:Animals; D002450:Cell Communication / Q000502:physiology*; D002461:Cell Line, Transformed / Q000502:physiology*; D002478:Cells, Cultured; D018920:Coculture Techniques; D018031:Connexin 43 / Q000172:deficiency*; D004553:Electric Conductivity; D017629:Gap Junctions / Q000502:physiology*; D051379:Mice; D018345:Mice, Knockout; D019061:src-Family Kinases / Q000378:metabolism*
D018031:Connexin 43; D019061:src-Family Kinases