title: Calyculin A and outward K+ channel currents in rat tail artery smooth muscle cells.
abstract: Protein dephosphorylation mediated by phosphatases represents an important mechanism for modulating the functions of the targeted proteins. Calyculin A has been extensively used as a specific inhibitor of protein phosphatases. However, the effect of calyculin A on K channel currents in vascular smooth muscle cells (SMCs) and the underlying mechanisms had been unknown. It was found in the current study that calyculin A inhibited the whole-cell outward K channel currents in rat tail artery SMCs in a concentration-dependent (median inhibitory concentration, 12.6 n ) and reversible fashion. The extracellular applied calyculin A induced a biphasic change in K current amplitude with an initial transient increase followed by a long-lasting inhibition (n = 6). The intracellularly applied calyculin A (100 nM ) caused a lesser inhibition (33 +/- 1%) of K channel currents than that caused by the extracellularly applied calyculin A (55.3 +/- 8% inhibition) and did not result in an initial increase in K channel currents. The inhibitory effect of the intracellularly applied calyculin A on K channel currents was reversed to a stimulatory effect after ATP was omitted from the intracellular solution. The K currents inhibited by calyculin A were conducted by the iberiotoxin-sensitive K channels in SMCs. Moreover, okadaic acid (0.03-3 microM ) did not cause any significant change in K(Ca) channel currents. In conclusion, calyculin A inhibited K(Ca) channel currents in vascular SMCs. This effect of calyculin A, however, was not mediated by the inhibition of protein phosphatases.
authors.affiliation: Department of Physiology, University of Saskatchewan, Saskatoon, SK, Canada.
authors.forename: Salma Toma
authors.initials: ST
authors.lastname: Hanna
authors.forename: Rui
authors.initials: R
authors.lastname: Wang
mesh_terms: D000818:Animals; D004594:Electrophysiology; D008297:Male; D008387:Marine Toxins; D009131:Muscle, Smooth, Vascular / Q000187:drug effects*; D010080:Oxazoles / Q000494:pharmacology*; D018408:Patch-Clamp Techniques; D015221:Potassium Channels / Q000187:drug effects*; D051381:Rats; D017207:Rats, Sprague-Dawley; D014662:Vasoconstrictor Agents / Q000494:pharmacology*
chemical_list: D008387:Marine Toxins; D010080:Oxazoles; D015221:Potassium Channels; D014662:Vasoconstrictor Agents; C059041:calyculin A