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(+) (K(V)) currents in freshly isolated rabbit coronary arterial smooth muscle cells, using a whole-cell patch clamp technique. H-89 inhibited the K(V) current in a concentration-dependent manner, with a K(d) value of 1.02 microM. However, the PKA inhibitors KT 5720 and Rp-8-CPT-cAMPS did not significantly alter the K(V) current or the inhibitory effects of H-89 on the K(V) current. Moreover, H-85, a structurally similar but inactive analog of H-89, showed similar inhibitory effects on the K(V) 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 K(V) current directly by blocking the pore cavity, an effect independent of PKA inhibition.
Son
Youn Kyoung
YK
Department of Physiology and National Research Laboratory for Cellular Signaling, Seoul National University College of Medicine, Seoul, Republic of Korea.
Park
Won Sun
WS
Kim
Sung Joon
SJ
Earm
Yung E
YE
Kim
Nari
N
Youm
Jae Boum
JB
Warda
Mohamad
M
Kim
Euiyong
E
Han
Jin
J
D000818:Animals; D002227:Carbazoles / Q000494:pharmacology; D003331:Coronary Vessels / Q000166:cytology / Q000187:drug effects; D000242:Cyclic AMP / Q000031:analogs & derivatives / Q000494:pharmacology; D017868:Cyclic AMP-Dependent Protein Kinases / Q000037:antagonists & inhibitors*; D005260:Female; D007211:Indoles / Q000494:pharmacology; D007546:Isoquinolines / Q000494:pharmacology*; D008297:Male; D009131:Muscle, Smooth, Vascular / Q000166:cytology* / Q000187:drug effects; D024642:Potassium Channels, Voltage-Gated / Q000187:drug effects*; D011758:Pyrroles / Q000494:pharmacology; D011817:Rabbits; D013449:Sulfonamides / Q000494:pharmacology*; D013873:Thionucleotides / Q000494:pharmacology
D002227:Carbazoles; D007211:Indoles; D007546:Isoquinolines; D024642:Potassium Channels, Voltage-Gated; D011758:Pyrroles; D013449:Sulfonamides; D013873:Thionucleotides; C071449:H 85; C015929:8-((4-chlorophenyl)thio)cyclic-3',5'-AMP; C057416:KT 5720; D000242:Cyclic AMP; D017868:Cyclic AMP-Dependent Protein Kinases; C063509:N-(2-(4-bromocinnamylamino)ethyl)-5-isoquinolinesulfonamide