The protein kinase A inhibitor, H-89, directly inhibits KATP and Kir channels in rabbit coronary arterial smooth muscle cells

Won Sun Park; Youn Kyoung Son; Nari Kim; Jae Boum Youm; Hyun Joo; Mohamad Warda; Jae-Hong Ko; Yung E Earm; Jin Han

doi:10.1016/j.bbrc.2005.12.116

The protein kinase A inhibitor, H-89, directly inhibits KATP and Kir channels in rabbit coronary arterial smooth muscle cells

Biochem Biophys Res Commun. 2006 Feb 24;340(4):1104-10. doi: 10.1016/j.bbrc.2005.12.116. Epub 2005 Dec 28.

Authors

Won Sun Park¹, Youn Kyoung Son, Nari Kim, Jae Boum Youm, Hyun Joo, Mohamad Warda, Jae-Hong Ko, Yung E Earm, Jin Han

Affiliation

¹ 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.

PMID: 16403438
DOI: 10.1016/j.bbrc.2005.12.116

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.

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

Animals
Cells, Cultured
Coronary Vessels / drug effects
Coronary Vessels / metabolism*
Cyclic AMP-Dependent Protein Kinases / antagonists & inhibitors*
Dose-Response Relationship, Drug
Ion Channel Gating / drug effects
Ion Channel Gating / physiology*
Isoquinolines / administration & dosage*
Membrane Potentials / drug effects
Membrane Potentials / physiology
Myocytes, Smooth Muscle / drug effects
Myocytes, Smooth Muscle / metabolism*
Potassium Channels / drug effects
Potassium Channels / physiology*
Potassium Channels, Inwardly Rectifying / drug effects
Potassium Channels, Inwardly Rectifying / physiology*
Protein Kinase Inhibitors / administration & dosage
Rabbits
Sulfonamides / administration & dosage*

Substances

Isoquinolines
Potassium Channels
Potassium Channels, Inwardly Rectifying
Protein Kinase Inhibitors
Sulfonamides
mitochondrial K(ATP) channel
Cyclic AMP-Dependent Protein Kinases
N-(2-(4-bromocinnamylamino)ethyl)-5-isoquinolinesulfonamide