Gap junctions between cells expressing connexin 43 or 32 show inverse permselectivity to adenosine and ATP.
Gap junctions, composed of proteins from the connexin family, are the only channels that directly connect the cytoplasm of adjacent cells to allow for the intercellular transfer of small hydrophilic molecules. Gap junctional communication is essential for proper development and health in animals and humans. Whereas the study of biological molecules that pass through gap junctions is extremely important, the identification of endogenous transjunctional metabolites is challenging. To help address this problem, we have developed a layered culture system to identify and quantitate the transfer of endogenous molecules that pass between cells through gap junctions. Using these techniques, we have identified several endogenous molecules that showed differential transfer between channels composed of Cx32 versus Cx43. For example, adenosine passed about 12-fold better through channels formed by Cx32. In contrast, AMP and ADP passed about 8-fold better, and ATP greater than 300-fold better, through channels formed by Cx43. Thus, addition of phosphate to adenosine appears to shift its relative permeability from channels formed by Cx32 to channels formed by Cx43. This suggests functional consequence because the energy status of a cell could be controlled via connexin expression and channel formation.
Department of Physiology and Biophysics, State University of New York, Stony Brook, New York 11794-8661, USA. gary.goldberg@sunysb.edu
Gary S
GS
Goldberg
Alonso P
AP
Moreno
Paul D
PD
Lampe
D000241:Adenosine / Q000378:metabolism*; D000244:Adenosine Diphosphate / Q000378:metabolism; D000249:Adenosine Monophosphate / Q000378:metabolism; D000818:Animals; D015153:Blotting, Western; D002478:Cells, Cultured; D002851:Chromatography, High Pressure Liquid; D004396:Coloring Agents / Q000494:pharmacology; D018031:Connexin 43 / Q000378:metabolism*; D017630:Connexins / Q000378:metabolism*; D017629:Gap Junctions; D008958:Models, Molecular; D010710:Phosphates / Q000378:metabolism; D010766:Phosphorylation; D011485:Protein Binding; D051381:Rats; D014162:Transfection; D000097002:Gap Junction beta-1 Protein
D000241:Adenosine; D000244:Adenosine Diphosphate; D000249:Adenosine Monophosphate; D004396:Coloring Agents; D018031:Connexin 43; D017630:Connexins; D010710:Phosphates; D000097002:Gap Junction beta-1 Protein