Calyculin A and outward K+ channel currents in rat tail artery smooth muscle cells.
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.
Hanna
Salma Toma
ST
Department of Physiology, University of Saskatchewan, Saskatoon, SK, Canada.
Wang
Rui
R
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*
D008387:Marine Toxins; D010080:Oxazoles; D015221:Potassium Channels; D014662:Vasoconstrictor Agents; C059041:calyculin A