title: The protein kinase A inhibitor, H-89, directly inhibits KATP and Kir channels in rabbit coronary arterial smooth muscle cells.
abstract: The effects of the protein kinase A (PKA) inhibitor H-89 on ATP-sensitive K+ (KATP) and inward rectifier K+ (Kir) currents were examined in rabbit coronary arterial smooth muscle cells using the patch clamp technique. The H-89, in a dose-dependent manner, inhibited KATP and Kir currents with apparent Kd values of 1.19+/-0.18 and 3.78+/-0.37 microM, respectively. H-85, which is considered as an inactive form of H-89, inhibited KATP and Kir currents, similar to the result of H-89. KATP and Kir currents were not affected by either Rp-8-CPT-cAMPs, which is a membrane-permeable selective PKA inhibitor, or KT 5720, which is also known as a PKA inhibitor. Also, these two drugs did not significantly alter the effects of H-89 on the KATP and Kir currents. These results suggest that H-89 directly inhibits the KATP and Kir currents of rabbit coronary arterial smooth muscle cells independently of PKA inhibition.
authors.affiliation: Mitochondrial Signaling Laboratory, Department of Physiology and Biophysics, College of Medicine, Biohealth Products Research Center, Cardiovascular and Metabolic disease Center, Inje University, Busan, Republic of Korea.
authors.forename: Won
authors.initials: W
authors.lastname: Sun Park
authors.forename: Youn
authors.initials: Y
authors.lastname: Kyoung Son
authors.forename: Nari
authors.initials: N
authors.lastname: Kim
authors.forename: Jae
authors.initials: J
authors.lastname: Boum Youm
authors.forename: Hyun
authors.initials: H
authors.lastname: Joo
authors.forename: Mohamad
authors.initials: M
authors.lastname: Warda
authors.forename: Jae-Hong
authors.initials: JH
authors.lastname: Ko
authors.forename: Yung E
authors.initials: YE
authors.lastname: Earm
authors.forename: Jin
authors.initials: J
authors.lastname: Han
mesh_terms: D000818:Animals; D002478:Cells, Cultured; D003331:Coronary Vessels / Q000187:drug effects / Q000378:metabolism*; D017868:Cyclic AMP-Dependent Protein Kinases / Q000037:antagonists & inhibitors*; D004305:Dose-Response Relationship, Drug; D015640:Ion Channel Gating / Q000187:drug effects / Q000502:physiology*; D007546:Isoquinolines / Q000008:administration & dosage*; D008564:Membrane Potentials / Q000187:drug effects / Q000502:physiology; D032389:Myocytes, Smooth Muscle / Q000187:drug effects / Q000378:metabolism*; D015221:Potassium Channels / Q000187:drug effects / Q000502:physiology*; D024661:Potassium Channels, Inwardly Rectifying / Q000187:drug effects / Q000502:physiology*; D047428:Protein Kinase Inhibitors / Q000008:administration & dosage; D011817:Rabbits; D013449:Sulfonamides / Q000008:administration & dosage*
chemical_list: D007546:Isoquinolines; D015221:Potassium Channels; D024661:Potassium Channels, Inwardly Rectifying; D047428:Protein Kinase Inhibitors; D013449:Sulfonamides; C117780:mitochondrial K(ATP) channel; D017868:Cyclic AMP-Dependent Protein Kinases; C063509:N-(2-(4-bromocinnamylamino)ethyl)-5-isoquinolinesulfonamide