REGULATION OF MOUSE CHOROID-PLEXUS APICAL CL- AND K+ CHANNELS BY SEROTONIN

Using patch-clamp techniques, we have characterized ion channels in th e apical membrane of the mouse choroid plexus epithelium and have exam ined the effect of serotonin on these channels. When the pipette conta ined 140 mM KCl and the bath contained NaCl Ringer solution, cell-atta ched patches revealed both Cl- and K+ channels. The Cl- channel was ac tivated by hyperpolarizing membrane potentials, and 70% were also acti vated by large depolarizing potentials (pipette potential, V(p), more negative than -40 mV). The channel exhibited linear current-voltage (I -V) relations with a conductance of 4 +/- 1 pS (n = 30), and a reversa l potential at V(p) = -14 +/- 1 mV (n = 30). The majority of the K cha nnels (84%) were activated by depolarizing membrane potentials. These exhibited linear I-V relations with a conductance of 18 +/- 1 pS (n 10 ) and a reversal potential at V(p) = - 51 +/- 8 mV (n = 10). Serotonin (10(-6) M) increased the open probability (P(o)) of active Cl-channel s (n = 20) by an order of magnitude at the resting potential (V(p) = 0 mV) as well as activating previously silent Cl- channels. In contrast , complete inhibition of K+ channel activity was observed in the major ity of experiments. There was a 30 s delay after exposure of the tissu e to serotonin, thereafter the K+ channel was rapidly inhibited (withi n 1 min) prior to the stimulation of the Cl- channel. Stimulation of t he Cl- channel by serotonin was abolished by mianserin (10(-3) M). We conclude that serotonin exerts its effect on apical Cl- channels via t he 5-HT1c receptor. The modulation of these channels by serotonin may be important to CSF secretion and its regulation.