Serotonin 5-HT2C receptors are highly expressed in choroid plexus epithelial cells (Boess & Martin, 1994). Single channel experiments have shown that serotonin reduces the open probability of an 18 pS K+ channel in mouse choroid plexus (Hung et al. 1993). In the present study we have examined the effects of serotonin on the delayed-rectifying K+ (Kv) conductance expressed in rat choroid plexus cells (Kotera & Brown, 1994).
The choroid plexus was isolated from the fourth ventricle of rats killed humanely by overdose of halothane inhalation. K+ channel activity was measured by conventional whole-cell methods using a K+-rich pipette solution. Kv currents were measured at membrane potentials between -60 and +60 mV. In control conditions the maximum current density observed at +60 mV was 16.4 ± 2.0 pA pF-1 (mean ± S.E.M.; n = 8), immediately after attaining the whole-cell recording. Channel ‘run-down’ caused the current to decrease slightly to 15.0 ± 1.8 pA pF-1 over 8 min (91 ± 3 % of the maximum). By contrast, superfusion of the cells for 8 min, with a bath solution containing 1 µM serotonin caused current to decrease to 48 ± 5 % of the maximum (n = 4). The current density after 8 min (8.2 ± 1.1 pA pF-1 was significantly less than that measured in the control experiments (P > 0.01 by Student’s t test for unpaired data).
Serotonin acts via 5-HT2C receptors to activate phospholipase C causing an increase in intracellular [Ca2+] and activation of protein kinase C (PKC). Previous studies have shown that the activity of the Kv channels in choroid plexus is not affected by changes in intracellular [Ca2+] (Kotera & Brown, 1994). The effects of activating PKC on the Kv conductance were therefore examined. Choroid plexus cells were pretreated for 10-20 min with: 1 µM serotonin, 500 nM phorbol 12-myristate 13-acetate (a phorbol ester which activates PKC) or 30 µM 1,2-dioctanoyl-sn-glycerol (a membrane permeable analogue of diacylglycerol). The maximum current at +60 mV was significantly reduced compared to control by serotonin and by both of the PKC activators (P < 0.01 by ANOVA).
In conclusion, serotonin inhibits the Kv channels in choroid plexus cells, possibly by acting on 5-HT2C receptors to activate PKC.
This work was supported by the Wellcome Trust.