Connexin channels, connexin mimetic peptides and ATP release.
Connexin hemichannels, that is, half gap junction channels (not connecting cells), have been implicated in the release of various messengers such as ATP and glutamate. We used connexin mimetic peptides, which are, small peptides mimicking a sequence on the connexin subunit, to investigate hemichannel functioning in endothelial cell lines. Short exposure (30 min) to synthetic peptides mimicking a sequence on the first or second extracellular loop of the connexin subunit strongly supressed ATP release and dye uptake triggered by either intracellular InsP(3) elevation or exposure to zero extracellular calcium, while gap junctional coupling was not affected under these conditions. The effect was dependent on the expression of connexin-43 in the cells. Connexin mimetic peptides thus appear to be interesting tools to distinguish connexin hemichannel from gap junction channel functioning. In addition, they are well suited to further explore the role of connexins in cellular release or uptake processes, to investigate hemichannel gating and to reveal new unknown functions of the large conductance hemichannel pathway between the cell and its environment. Work performed up to now with these peptides should be re-interpreted in terms of these new findings.
Leybaert
Luc
L
Department of Physiology and Pathophysiology, Ghent University, Ghent, Belgium. Luc.Leybaert@UGent.be
Braet
Katleen
K
Vandamme
Wouter
W
Cabooter
Liesbet
L
Martin
Patricia E M
PE
Evans
W Howard
WH
D000255:Adenosine Triphosphate / Q000378:metabolism*; D000595:Amino Acid Sequence; D000818:Animals; D002118:Calcium / Q000378:metabolism; D002450:Cell Communication / Q000187:drug effects*; D002478:Cells, Cultured; D017630:Connexins / Q000378:metabolism*; D042783:Endothelial Cells / Q000378:metabolism; D017629:Gap Junctions / Q000502:physiology*; D006367:HeLa Cells; D006801:Humans; D008969:Molecular Sequence Data; D010455:Peptides / Q000494:pharmacology*; D011419:Propidium; D014409:Tumor Necrosis Factor-alpha / Q000378:metabolism
D017630:Connexins; D010455:Peptides; D014409:Tumor Necrosis Factor-alpha; D011419:Propidium; D000255:Adenosine Triphosphate; D002118:Calcium