Inhibition of a K+ conductance by the phosphatase inhibitor calyculin A in rat distal colon.
Basal membrane permeability of epithelial cells from the lower third and the middle of rat colonic crypts is dominated by a K+ conductance as shown by ion replacement experiments. Calyculin A, an inhibitor of protein phosphatases, induced a depolarization of these cells. The depolarization was concomitant with an inhibition of membrane current. The current inhibited by calyculin A had a reversal potential identical with the theoretical K+ equilibrium potential indicating that the drug inhibits a basal K+ conductance. The efficiency of calyculin A was comparable with that of other well-known K+ channel blockers such as Ba2+, tetraethylammonium or quinine. In the intact tissue, calyculin A exerted an inhibitory action on forskolin-induced anion secretion, an effect which may be explained by the decrease in the driving force for Cl- exit after inhibition of cellular K+ conductance. Together with previous results, these data suggest an inhibition of epithelial K+ conductance by phosphorylation.
Institut für Veterinär-Physiologie, Justus-Liebig-Universität Giessen, Germany.
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Schultheiss
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Diener
D000818:Animals; D003106:Colon / Q000166:cytology / Q000187:drug effects* / Q000502:physiology; D000242:Cyclic AMP / Q000502:physiology; D004553:Electric Conductivity; D004791:Enzyme Inhibitors / Q000494:pharmacology*; D005260:Female; D019833:Genistein / Q000494:pharmacology; D066298:In Vitro Techniques; D007413:Intestinal Mucosa / Q000166:cytology / Q000187:drug effects / Q000502:physiology; D017136:Ion Transport / Q000502:physiology; D008387:Marine Toxins; D019319:Okadaic Acid / Q000494:pharmacology; D010080:Oxazoles / Q000494:pharmacology*; D010749:Phosphoprotein Phosphatases / Q000037:antagonists & inhibitors*; D026902:Potassium Channel Blockers; D015221:Potassium Channels / Q000502:physiology; D011505:Protein-Tyrosine Kinases / Q000037:antagonists & inhibitors; D051381:Rats; D017208:Rats, Wistar
D004791:Enzyme Inhibitors; D008387:Marine Toxins; D010080:Oxazoles; D026902:Potassium Channel Blockers; D015221:Potassium Channels; D019319:Okadaic Acid; C059041:calyculin A; D019833:Genistein; D000242:Cyclic AMP; D011505:Protein-Tyrosine Kinases; D010749:Phosphoprotein Phosphatases