ATP-sensitive potassium channel regulates astrocytic gap junction permeability by a Ca2+-independent mechanism.
Using the scrape-loading technique in cultured astrocytes, we show that sulfonylureas such as tolbutamide and glybenzcyclamide, which inhibit the ATP-sensitive K+ channel, prevent the inhibition of gap junction permeability caused by several structurally unrelated uncouplers such as oleic acid, arachidonic acid, endothelin-1, octanol, and alpha-glycyrrhetinic acid. When the intracellular level of Ca2+ was diminished, all the uncouplers tested were still able to inhibit gap junction communication, indicating that their inhibitory effect was not mediated by Ca2+. In addition, tolbutamide and glybenzcyclamide prevented the inhibitory effect of these uncouplers in Ca(2+)-depleted astrocytes, suggesting that the inhibition of the ATP-sensitive K+ channel increases gap junction permeability through a Ca(2+)-independent mechanism. The activation of the ATP-sensitive K+ channel caused by potassium channel openers such as diazoxide and pinacidil led to the inhibition of gap junction communication and overcame the effect of sulfonylureas. These results suggest that the ATP-sensitive K+ channel regulates gap junctional permeability.
Velasco
A
A
Departamento de Bioquímica y Biología Molecular, Facultad de Farmacia, Universidad de Salamanca, Spain.
Tabernero
A
A
Granda
B
B
Medina
J M
JM
D000255:Adenosine Triphosphate / Q000502:physiology*; D000818:Animals; D001253:Astrocytes / Q000187:drug effects / Q000378:metabolism*; D002118:Calcium / Q000502:physiology*; D002478:Cells, Cultured; D003981:Diazoxide / Q000494:pharmacology; D017629:Gap Junctions / Q000187:drug effects / Q000378:metabolism*; D007425:Intracellular Membranes / Q000378:metabolism; D009994:Osmolar Concentration; D010539:Permeability / Q000187:drug effects; D020110:Pinacidil / Q000494:pharmacology; D015221:Potassium Channels / Q000187:drug effects / Q000502:physiology*; D051381:Rats; D017208:Rats, Wistar; D013453:Sulfonylurea Compounds / Q000037:antagonists & inhibitors / Q000494:pharmacology; D014475:Uncoupling Agents / Q000494:pharmacology
D015221:Potassium Channels; D013453:Sulfonylurea Compounds; D014475:Uncoupling Agents; D020110:Pinacidil; D000255:Adenosine Triphosphate; D003981:Diazoxide; D002118:Calcium