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

The effects of the protein kinase A (PKA) inhibitor H-89 on ATP-sensitive K+ (K-ATP) 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 K-ATP and Kir currents with apparent K-d values of 1.19 +/- 0.18 and 3.78 +/- 0.37 mu M, respectively. H-85, which is considered as an inactive form of H-89, inhibited K-ATP and Kir currents, similar to the result of H-89. K-ATP 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 K-ATP and Kir currents. These results suggest that H-89 directly inhibits the K-ATP and Kir currents of rabbit coronary arterial smooth muscle cells independently of PKA inhibition. (c) 2005 Elsevier Inc. All rights reserved.