Proceedings of The Physiological Society

Puerto de la Cruz, Tenerife (2003) J Physiol 548P, P55

Poster Communications

Serotonin inhibits the delayed-rectifying K+ (Kv) conductance in the epithelial cells of choroid plexus isolated from the rat

Tracey Speake, Jon D. Kibble and Peter D. Brown

School of Biological Sciences, University of Manchester, Manchester M13 9PT, UK

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.

Where applicable, experiments conform with Society ethical requirements