Kv1.1 and Kv1.3 channels contribute to the delayed-rectifying K+conductance in rat choroid plexus epithelial cells

Abstract

The choroid plexuses secrete, and maintain the composition of, the cerebrospinal fluid. K+channels play an important role in these processes. In this study the molecular identity and properties of the delayed-rectifying K+(Kv) conductance in rat choroid plexus epithelial cells were investigated. Whole cell K+currents were significantly reduced by 10 nM dendrotoxin-K and 1 nM margatoxin, which are specific inhibitors of Kv1.1 and Kv1.3 channels, respectively. A combination of dendrotoxin-K and margatoxin caused a depolarization of the membrane potential in current-clamp experiments. Western blot analysis indicated the presence of Kv1.1 and Kv1.3 proteins in the choroid plexus. Furthermore, the Kv1.3 and Kv1.1 proteins appear to be expressed in the apical membrane of the epithelial cells in immunocytochemical studies. The Kv conductance was inhibited by 1 μM serotonin (5-HT), with maximum inhibition to 48% of control occurring in 8 min ( P < 0.05 by Student's t-test for paired data). Channel inhibition by 5-HT was prevented by the 5-HT2Cantagonist mesulergine (300 nM). It was also attenuated in the presence of calphostin C (a protein kinase C inhibitor). The conductance was partially inhibited by 1,2-dioctanoyl- sn-glycerol and phorbol 12-myristate 13-acetate, both of which activate protein kinase C. These data suggest that 5-HT acts at 5-HT2Creceptors to activate protein kinase C, which inhibits the Kv channels. In conclusion, Kv1.1 and Kv1.3 channels make a significant contribution to K+efflux at the apical membrane of the choroid plexus.