Document Detail

Direct measurement of cyclic AMP diffusion and signaling through connexin43 gap junctional channels.
MedLine Citation:
PMID:  17150212     Owner:  NLM     Status:  MEDLINE    
Gap junctions (GJ) are clusters of transmembrane channels that allow direct cell-to-cell transfer of ions and small molecules. The GJ-permeant signaling molecule cAMP is of particular interest because of its numerous cellular effects. However, to assess the biological relevance of GJ-mediated cAMP transfer, quantitative aspects must be determined. Here we employed cAMP indicators based on fluorescence resonance energy transfer (FRET) to study propagation of cAMP signals to neighbor cells through connexin43 (Cx43)-based gap junctions in Rat-1 cells quantitatively. Intracellular cAMP levels were selectively raised in single cells by either photorelease of caged cAMP or stimulation of G(s)-coupled receptors. cAMP elevations spread to adjacent cells within seconds in a Cx43-dependent manner. We determined that Rat-1 cells follow cAMP rises in surrounding monolayer cells to approx. 40% in amplitude. This degree of cAMP transfer sufficed to evoke a well-characterized response to cAMP in neighbor cells, i.e. the PKA-mediated phosphorylation of the ER transcription factor in A431 carcinoma cells. We conclude that contacting cells can cooperatively regulate cAMP-sensitive processes via gap junctional diffusion of cAMP.
Bas Ponsioen; Leonie van Zeijl; Wouter H Moolenaar; Kees Jalink
Publication Detail:
Type:  Journal Article; Research Support, Non-U.S. Gov't     Date:  2006-11-06
Journal Detail:
Title:  Experimental cell research     Volume:  313     ISSN:  0014-4827     ISO Abbreviation:  Exp. Cell Res.     Publication Date:  2007 Jan 
Date Detail:
Created Date:  2007-01-12     Completed Date:  2007-03-09     Revised Date:  -    
Medline Journal Info:
Nlm Unique ID:  0373226     Medline TA:  Exp Cell Res     Country:  United States    
Other Details:
Languages:  eng     Pagination:  415-23     Citation Subset:  IM    
Divisions of Cell Biology, The Netherlands Cancer Institute Plesmanlaan 121 1066 CX Amsterdam, The Netherlands.
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MeSH Terms
Biosensing Techniques
Cell Communication*
Cells, Cultured
Connexin 43 / genetics,  physiology*
Cyclic AMP / analysis*,  metabolism*
Fibroblasts / chemistry,  cytology,  metabolism
Fluorescence Resonance Energy Transfer
Gap Junctions / physiology*
Phosphoric Diester Hydrolases / metabolism
Receptors, G-Protein-Coupled / agonists
Signal Transduction
Transcription Factors
Reg. No./Substance:
0/Connexin 43; 0/Receptors, G-Protein-Coupled; 0/Transcription Factors; 60-92-4/Cyclic AMP; EC 3.1.4.-/Phosphoric Diester Hydrolases

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