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.
Tohda
M
M
Department of Pharmacology, Faculty of Pharmaceutical Sciences, Hokkaido University, Sapporo, Japan.
Nakamura
J
J
Hidaka
H
H
Nomura
Y
Y
D019307:1-(5-Isoquinolinesulfonyl)-2-Methylpiperazine / Q000031:analogs & derivatives*; D000818:Animals; D017871:Calcium-Calmodulin-Dependent Protein Kinases; D018118:Chloride Channels; D002712:Chlorides / Q000378:metabolism*; D007546:Isoquinolines / Q000494:pharmacology*; D008297:Male; D008565:Membrane Proteins / Q000187:drug effects*; D009865:Oocytes / Q000378:metabolism; D010766:Phosphorylation; D010879:Piperazines / Q000494:pharmacology*; D047428:Protein Kinase Inhibitors; D011494:Protein Kinases / Q000502:physiology; D051381:Rats; D011919:Rats, Inbred Strains; D012701:Serotonin / Q000494:pharmacology*; D014981:Xenopus
D018118:Chloride Channels; D002712:Chlorides; D007546:Isoquinolines; D008565:Membrane Proteins; D010879:Piperazines; D047428:Protein Kinase Inhibitors; D012701:Serotonin; C063302:KN 62; D019307:1-(5-Isoquinolinesulfonyl)-2-Methylpiperazine; D011494:Protein Kinases; D017871:Calcium-Calmodulin-Dependent Protein Kinases