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-isoquinolinesulfo namide), a potent and selective inhibitor of protein kinase A (PKA), were e xamined on Kv1.3 channels stably expressed in Chinese hamster ovary (CHO) c ells using the patch clamp technique. In whole-cell recordings, H-89 decrea sed Kv1.3 currents and accelerated the decay rate of current inactivation i n a concentration-dependent manner with an IC50 value of 1.70 muM. These ef fects 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 appl ied to the cytoplasmic surface also inhibited Kv1.3 currents in excised ins ide-out parches. These findings suggest that H-89 inhibits Kv1.3 currents i ndependently of PKA. (C) 2001 Elsevier Science Inc. All rights reserved.