Direct inhibition of a PKA inhibitor, H-89 on KV channels in rabbit coronary arterial smooth muscle cells Youn Kyoung Sona, 1, Won Sun Parkb, 1, Sung Joon Kima, Yung E. Earma, Nari Kimb, Jae Boum Youmb, Mohamad Wardab, Euiyong Kimb and Jin Hanb, , aDepartment of Physiology and National Research Laboratory for Cellular Signaling, Seoul National University College of Medicine, Seoul, Republic of Korea bMitochondrial 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 Received 9 January 2006. Available online 23 January 2006. Abstract 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 Kd value of 1.02 μM. 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. Keywords: Protein kinase A; H-89; Voltage-dependent K+ currents; Coronary arterial smooth muscle cells