Direct inhibition of a PKA inhibitor, H-89 on KV channels in rabbit coronary arterial smooth muscle cells

We examined the effects of the protein kinase A (PKA) inhibitor H-89 on voltage-dependent K+ (Kv) currents in freshly isolated rabbit coronary arterial smooth muscle cells, using a whole-cell patch clamp technique. H-89 inhibited the Kv current in a concentration-dependent manner, with a K-d value of 1.02 mu M. However, the PKA inhibitors KT 5720 and Rp-8-CPT-cAMPS did not significantly alter the Kv current or the inhibitory effects of H-89 on the Kv current. Moreover, H-85, a structurally similar but inactive analog of H-89, showed similar inhibitory effects on the Kv 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 Kv current directly by blocking the pore cavity, an effect independent of PKA inhibition. (c) 2006 Elsevier Inc. All rights reserved.