Regulation of mouse choroid plexus apical Cl- and K+ channels by serotonin.
Using patch-clamp techniques, we have characterized ion channels in the apical membrane of the mouse choroid plexus epithelium and have examined the effect of serotonin on these channels. When the pipette contained 140 mM KCl and the bath contained NaCl Ringer solution, cell-attached patches revealed both Cl- and K+ channels. The Cl- channel was activated by hyperpolarizing membrane potentials, and 70% were also activated by large depolarizing potentials (pipette potential, Vp, 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 reversal potential at Vp = -14 +/- 1 mV (n = 30). The majority of the K+ channels (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 Vp = -51 +/- 8 mV (n = 10). Serotonin (10(-6) M) increased the open probability (Po) of active Cl- channels (n = 20) by an order of magnitude at the resting potential (Vp = 0 mV) as well as activating previously silent Cl- channels. In contrast, complete inhibition of K+ channel activity was observed in the majority of experiments. There was a 30 s delay after exposure of the tissue to serotonin, thereafter the K+ channel was rapidly inhibited (within 1 min) prior to the stimulation of the Cl- channel. Stimulation of the Cl- channel by serotonin was abolished by mianserin (10(-3) M). We conclude that serotonin exerts its effect on apical Cl- channels via the 5-HT1c receptor. The modulation of these channels by serotonin may be important to CSF secretion and its regulation.
Hung
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BC
Department of Physiology, University of California, School of Medicine, Los Angeles 90024-1751.
Loo
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DD
Wright
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EM
D000818:Animals; D018118:Chloride Channels / Q000187:drug effects*; D002831:Choroid Plexus / Q000187:drug effects*; D008564:Membrane Potentials / Q000187:drug effects; D008803:Mianserin / Q000494:pharmacology; D051379:Mice; D015221:Potassium Channels / Q000187:drug effects*; D012701:Serotonin / Q000494:pharmacology*
D018118:Chloride Channels; D015221:Potassium Channels; D008803:Mianserin; D012701:Serotonin