title: Direct modulation of Ca(2+)-activated K(+) current by H-89 in rabbit coronary arterial smooth muscle cells.
abstract: The effects of H-89, a potent and selective inhibitor of protein kinase A (PKA) on Ca(2+)-activated K(+) (BK(Ca)) channels in coronary arterial smooth muscle cells were examined using a patch-clamp technique. In inside-out configuration, H-89 increased the NP(o) of the BK(Ca) channel, but it reduced the dwell time of BK(Ca) currents. In whole-cell configuration, H-89 markedly increased BK(Ca) currents in a concentration-dependent manner. The EC(50) was 0.470+/-0.0741 microM based on dwell time, 0.582+/-0.0691 microM based on the NP(o), and 0.519+/-0.0295 microM based on the whole-cell current, respectively. H-85, which is an inactive form of H-89, increased BK(Ca) currents, similar to the result of H-89. The other PKA inhibitors (Rp-8-CPT-cAMPs and KT 5720) and protein phosphatase inhibitor (okadaic acid, 1 microM) had little effect on BK(Ca) currents and did not significantly alter the stimulatory effects of 1 microM H-89. These findings suggest that H-89 increases the BK(Ca) current independently of PKA.
authors.affiliation: Department of Physiology and Biophysics, College of Medicine, Cardiovascular and Metabolic Disease Research Center, 633-165 Gaegeum-Dong, Busanjin-Gu, Busan 613-735, Republic of Korea.
authors.forename: Won Sun
authors.initials: WS
authors.lastname: Park
authors.forename: Youn Kyoung
authors.initials: YK
authors.lastname: Son
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: Jae-Hong
authors.initials: JH
authors.lastname: Ko
authors.forename: Eun A
authors.initials: EA
authors.lastname: Ko
authors.forename: Sung Hyun
authors.initials: SH
authors.lastname: Kang
authors.forename: Euiyong
authors.initials: E
authors.lastname: Kim
authors.forename: Yung E
authors.initials: YE
authors.lastname: Earm
authors.forename: Jin
authors.initials: J
authors.lastname: Han
mesh_terms: D000818:Animals; D002227:Carbazoles / Q000494:pharmacology; D003326:Coronary Circulation / Q000187:drug effects; D003331:Coronary Vessels / Q000187:drug effects / Q000378:metabolism; D000242:Cyclic AMP / Q000031:analogs & derivatives / Q000494:pharmacology; D017868:Cyclic AMP-Dependent Protein Kinases / Q000037:antagonists & inhibitors; D004305:Dose-Response Relationship, Drug; D004791:Enzyme Inhibitors / Q000494:pharmacology; D066298:In Vitro Techniques; D007211:Indoles / Q000494:pharmacology; D007546:Isoquinolines / Q000494:pharmacology*; D008564:Membrane Potentials / Q000187:drug effects; D009131:Muscle, Smooth, Vascular / Q000187:drug effects* / Q000378:metabolism; D019319:Okadaic Acid / Q000494:pharmacology; D018408:Patch-Clamp Techniques; D010749:Phosphoprotein Phosphatases / Q000037:antagonists & inhibitors; D024681:Potassium Channels, Calcium-Activated / Q000187:drug effects* / Q000378:metabolism; D047428:Protein Kinase Inhibitors / Q000494:pharmacology*; D011758:Pyrroles / Q000494:pharmacology; D011817:Rabbits; D013449:Sulfonamides / Q000494:pharmacology*; D013873:Thionucleotides / Q000494:pharmacology; D013997:Time Factors; D014655:Vascular Resistance / Q000187:drug effects
chemical_list: D002227:Carbazoles; D004791:Enzyme Inhibitors; D007211:Indoles; D007546:Isoquinolines; D024681:Potassium Channels, Calcium-Activated; D047428:Protein Kinase Inhibitors; D011758:Pyrroles; D013449:Sulfonamides; D013873:Thionucleotides; D019319:Okadaic Acid; C015929:8-((4-chlorophenyl)thio)cyclic-3',5'-AMP; C057416:KT 5720; D000242:Cyclic AMP; D017868:Cyclic AMP-Dependent Protein Kinases; D010749:Phosphoprotein Phosphatases; C063509:N-(2-(4-bromocinnamylamino)ethyl)-5-isoquinolinesulfonamide