Selective downregulation of an inactivating K+ conductance by analogues of cAMP in mouse Schwann cells.
1. Voltage-dependent K+ conductances on Schwann cells in organotypic cultures of mouse dorsal root ganglia were classified as inactivating or sustained (responsible for currents IA and IK, respectively). IA is known to be much reduced on Schwann cells that contact neurites. 2. In the absence of neurones, IA and IK were present. IA, but not IK, was markedly reduced (by 80% after 105 h of treatment) by 2 mM 8-(4-chlorophenylthio)-cAMP (cpt-cAMP), a weakly hydrolysable analogue of cAMP. The effect did not appear for at least 2 h and was maximal after about 100 h. 3. The effect of 1 mM cpt-cAMP was abolished in the presence of an inhibitor of protein kinases, N-[2-bromocinnamyl(amino)ethyl]-5-isoquinolinesulphonamide (H-89, 10 microM). 4. Other analogues of cAMP, but not an analogue of cGMP (8-bromo-cGMP), also reduced IA. 5. We conclude that IA, but not IK, can be downregulated by activation of the protein kinase A pathway.
Despeyroux
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Institut National de la Santé et de la Recherche Médicale, Unité de Neurobiologie Intégrative, U394, Bordeaux, France.
Beaudu-Lange
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C
Coles
J A
JA
Amédée
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D015124:8-Bromo Cyclic Adenosine Monophosphate / Q000494:pharmacology; D000818:Animals; D000242:Cyclic AMP / Q000031:analogs & derivatives* / Q000494:pharmacology / Q000502:physiology; D017868:Cyclic AMP-Dependent Protein Kinases / Q000037:antagonists & inhibitors; D006152:Cyclic GMP / Q000031:analogs & derivatives / Q000494:pharmacology; D015536:Down-Regulation; D004791:Enzyme Inhibitors / Q000494:pharmacology; D005727:Ganglia, Spinal / Q000187:drug effects / Q000196:embryology; D051379:Mice; D015221:Potassium Channels / Q000187:drug effects / Q000502:physiology*; D012583:Schwann Cells / Q000187:drug effects / Q000502:physiology*; D013329:Structure-Activity Relationship; D013873:Thionucleotides / Q000494:pharmacology
D004791:Enzyme Inhibitors; D015221:Potassium Channels; D013873:Thionucleotides; D015124:8-Bromo Cyclic Adenosine Monophosphate; C016276:8-bromocyclic GMP; C015929:8-((4-chlorophenyl)thio)cyclic-3',5'-AMP; D000242:Cyclic AMP; D017868:Cyclic AMP-Dependent Protein Kinases; D006152:Cyclic GMP