Inhibitory effects of KN-62, a specific inhibitor of Ca/calmodulin-dependent protein kinase II, on serotonin-evoked C1-current and 36-C1-efflux in Xenopus oocytes.

To clarify the details of the involvement of Ca(2+)-calmodulin in gating of C1-channels, effects of a novel calmodulin-dependent protein kinase II (CaMK II) inhibitor, KN-62, on C1-current and C1-efflux induced by serotonin (5-HT) were investigated in Xenopus oocyte injected with rat brain mRNA. 5-HT evoked inward current on voltage clamp condition at -60 mV in a concentration-dependent manner. The 5-HT (1 microM)-evoked current was blocked by preperfusion with 1 microM KN-62 also inhibited acetylcholine- and inositol 1,4,5-trisphosphate-evoked current. Furthermore, 5-HT enhanced Cl- efflux about 2.5-fold from the oocyte preinjected with 36Cl-, and the effects were inhibited by KN-62 as well. These results suggest that CaMK II is activated by Ca(2+)-calmodulin and opens Cl- channels to induce CL- efflux in Xenopus oocytes.