title: Direct inhibition of a PKA inhibitor, H-89 on KV channels in rabbit coronary arterial smooth muscle cells.
abstract: We examined the effects of the protein kinase A (PKA) inhibitor H-89 on voltage-dependent K(+) (K(V)) currents in freshly isolated rabbit coronary arterial smooth muscle cells, using a whole-cell patch clamp technique. H-89 inhibited the K(V) current in a concentration-dependent manner, with a K(d) value of 1.02 microM. However, the PKA inhibitors KT 5720 and Rp-8-CPT-cAMPS did not significantly alter the K(V) current or the inhibitory effects of H-89 on the K(V) current. Moreover, H-85, a structurally similar but inactive analog of H-89, showed similar inhibitory effects on the K(V) channel. H-89 had no effect on the voltage-dependency of activation or inactivation, or on recovery kinetics. These results suggest that in rabbit coronary arterial smooth muscle cells, H-89 inhibits the K(V) current directly by blocking the pore cavity, an effect independent of PKA inhibition.
authors.affiliation: Department of Physiology and National Research Laboratory for Cellular Signaling, Seoul National University College of Medicine, Seoul, Republic of Korea.
authors.forename: Youn Kyoung
authors.initials: YK
authors.lastname: Son
authors.forename: Won Sun
authors.initials: WS
authors.lastname: Park
authors.forename: Sung Joon
authors.initials: SJ
authors.lastname: Kim
authors.forename: Yung E
authors.initials: YE
authors.lastname: Earm
authors.forename: Nari
authors.initials: N
authors.lastname: Kim
authors.forename: Jae Boum
authors.initials: JB
authors.lastname: Youm
authors.forename: Mohamad
authors.initials: M
authors.lastname: Warda
authors.forename: Euiyong
authors.initials: E
authors.lastname: Kim
authors.forename: Jin
authors.initials: J
authors.lastname: Han
mesh_terms: D000818:Animals; D002227:Carbazoles / Q000494:pharmacology; D003331:Coronary Vessels / Q000166:cytology / Q000187:drug effects; D000242:Cyclic AMP / Q000031:analogs & derivatives / Q000494:pharmacology; D017868:Cyclic AMP-Dependent Protein Kinases / Q000037:antagonists & inhibitors*; D005260:Female; D007211:Indoles / Q000494:pharmacology; D007546:Isoquinolines / Q000494:pharmacology*; D008297:Male; D009131:Muscle, Smooth, Vascular / Q000166:cytology* / Q000187:drug effects; D024642:Potassium Channels, Voltage-Gated / Q000187:drug effects*; D011758:Pyrroles / Q000494:pharmacology; D011817:Rabbits; D013449:Sulfonamides / Q000494:pharmacology*; D013873:Thionucleotides / Q000494:pharmacology
chemical_list: D002227:Carbazoles; D007211:Indoles; D007546:Isoquinolines; D024642:Potassium Channels, Voltage-Gated; D011758:Pyrroles; D013449:Sulfonamides; D013873:Thionucleotides; C071449:H 85; C015929:8-((4-chlorophenyl)thio)cyclic-3',5'-AMP; C057416:KT 5720; D000242:Cyclic AMP; D017868:Cyclic AMP-Dependent Protein Kinases; C063509:N-(2-(4-bromocinnamylamino)ethyl)-5-isoquinolinesulfonamide