Inhibition of Kv1.3 channels by H-89 (N--[2-(p-bromocinnamylamino)ethyl]-5-isoquinolinesulfonamide) independent of protein kinase A.
The effects of H-89 (N-[2-(p-bromocinnamylamino)ethyl]-5-isoquinolinesulfonamide), a potent and selective inhibitor of protein kinase A (PKA), were examined on Kv1.3 channels stably expressed in Chinese hamster ovary (CHO) cells using the patch clamp technique. In whole-cell recordings, H-89 decreased Kv1.3 currents and accelerated the decay rate of current inactivation in a concentration-dependent manner with an IC(50) value of 1.70 microM. These effects were completely reversible after washout. Intracellular infusion with PKA inhibitors, adenosine 3', 5'-cyclic phosphorothioate-Rp (Rp-cAMPS) or protein kinase A inhibitor 5-24 (PKI 5-24) had no effect on Kv1.3 currents and did not prevent the inhibitory action of H-89 on the current. H-89 applied to the cytoplasmic surface also inhibited Kv1.3 currents in excised inside-out patches. These findings suggest that H-89 inhibits Kv1.3 currents independently of PKA.
Choi
J
J
Department of Physiology, The Catholic University of Korea, College of Medicine, 505 Banpo-dong, Socho-gu, 137-701, Seoul, South Korea.
Choi
B H
BH
Hahn
S J
SJ
Yoon
S H
SH
Min
D S
DS
Jo
Y
Y
Kim
M
M
D000818:Animals; D016466:CHO Cells; D006224:Cricetinae; D017868:Cyclic AMP-Dependent Protein Kinases / Q000037:antagonists & inhibitors / Q000378:metabolism*; D004791:Enzyme Inhibitors / Q000494:pharmacology; D007546:Isoquinolines / Q000494:pharmacology*; D051664:Kv1.3 Potassium Channel; D026902:Potassium Channel Blockers; D015221:Potassium Channels / Q000378:metabolism; D024642:Potassium Channels, Voltage-Gated; D013449:Sulfonamides
D004791:Enzyme Inhibitors; D007546:Isoquinolines; D051664:Kv1.3 Potassium Channel; D026902:Potassium Channel Blockers; D015221:Potassium Channels; D024642:Potassium Channels, Voltage-Gated; D013449:Sulfonamides; D017868:Cyclic AMP-Dependent Protein Kinases; C063509:N-(2-(4-bromocinnamylamino)ethyl)-5-isoquinolinesulfonamide