Staurosporine inhibits voltage-dependent K+ current through a PKC-independent mechanism in isolated coronary arterial smooth muscle cells.
We examined the effects of the protein kinase C (PKC) inhibitor staurosporine (ST) on voltage-dependent K (KV) channels in rabbit coronary arterial smooth muscle cells. ST inhibited the KV current in a dose-dependent manner with a Kd value of 1.3 microM. The inhibition of the KV current by ST was voltage-dependent between -30 and +10 mV. The additive inhibition of the KV current by ST was voltage-dependent throughout the activation voltage range. The rate constants of association and dissociation of ST were 0.63 microM s and 0.92 s, respectively. ST produced use-dependent inhibition of the KV current. ST shifted the activation curve to more positive potentials but did not have any significant effect on the voltage dependence of the inactivation curve. ST did not have any significant effects on other types of K channel. Another PKC inhibitor, chelerythrine, and PKA inhibitor peptide (PKA-IP) had little effect on the KV current. These results suggest that ST interacts with KV channels that are in the closed state and that ST inhibits KV channels in the open state in a manner that is phosphorylation-independent and voltage-, time-, and use-dependent.
Park
Won Sun
WS
Department of Physiology and National Research Laboratory for Cellular Signaling, Seoul National University College of Medicine, Seoul, Korea.
Son
Youn Kyoung
YK
Han
Jin
J
Kim
Nari
N
Ko
Jae-Hong
JH
Bae
Young Min
YM
Earm
Yung E
YE
D000465:Algorithms; D000470:Alkaloids; D000818:Animals; D053119:Benzophenanthridines; D002469:Cell Separation; D003331:Coronary Vessels / Q000187:drug effects / Q000201:enzymology; D017868:Cyclic AMP-Dependent Protein Kinases / Q000037:antagonists & inhibitors; D004305:Dose-Response Relationship, Drug; D004791:Enzyme Inhibitors / Q000494:pharmacology*; D005260:Female; D066298:In Vitro Techniques; D007700:Kinetics; D008297:Male; D009131:Muscle, Smooth, Vascular / Q000187:drug effects / Q000201:enzymology*; D018408:Patch-Clamp Techniques; D010617:Phenanthridines / Q000494:pharmacology; D010766:Phosphorylation; D026902:Potassium Channel Blockers; D024642:Potassium Channels, Voltage-Gated / Q000187:drug effects / Q000378:metabolism*; D011493:Protein Kinase C / Q000502:physiology*; D011817:Rabbits; D019311:Staurosporine / Q000494:pharmacology*
D000470:Alkaloids; D053119:Benzophenanthridines; D004791:Enzyme Inhibitors; D010617:Phenanthridines; D026902:Potassium Channel Blockers; D024642:Potassium Channels, Voltage-Gated; C016299:chelerythrine; D017868:Cyclic AMP-Dependent Protein Kinases; D011493:Protein Kinase C; D019311:Staurosporine