Channels

The 5-HT2C receptor has been shown to modulate the activities of various K+ channels; for example, the receptor closes K+ channels in the apical membrane of the mouse choroid plexus epithelium (Hung et al. 1993). When the 5-HT2C receptor was coexpressed with rat cerebral cortex K+ channels in Xenopus laevis oocytes, activation of the receptor also resulted in closing of the K+ channels in a Ca2+ -independent manner. The coupling between the receptors and channels appears to be mediated by the inositol phospholipid second messenger pathway (Panicker et al. 1991). Another study has suggested that the suppression of K+ currents by the 5-HT2C receptor coexpressed with a cloned mouse brain K+ channel in Xenopus laevis oocytes, occurs through a novel mechanism, which is independent of A- or C-type protein kinases, but which involves a Ca2+/calmodulin-activated phosphatase (Hoger et al. 1991).

DiMagno et al. showed that the 5-HT2C receptor, when coexpressed in Xenopus oocytes with rat brain mRNA, could inhibit an inwardly rectified, Ba2+ -sensitive K+ conductance through a PKC-dependent pathway (DiMagno et al. 1996). When coexpressed in Xenopus oocytes, the 5-HT2C receptor also suppresses the activity of the Shaker-related K+ gene Kv1.3, which encodes the type n K+ channel. This effect on Kv1.3 currents occurs via activation of a PTX-sensitive G protein and a subsequent rise in intracellular Ca2+ but not via PKC, Ca2+/calmodulin, or phosphatases (Aiyar et al. 1993). Timpe and Fantl used a similar system to show that the 5-HT2C receptor suppressed the activity of the voltage-activated K+ channel Kv1.5 through a PLC-dependent pathway (Timpe and Fantl 1994). Speake et al. provided functional and immunocytochemical evidence for the presence of Kv1.1 and Kv1.3 K+ channels in choroid plexus epithelial cells and demonstrated that the 5-HT2C receptor inhibits the Kv conductance by stimulating PKC (Speake et al. 2004). This regulation of K+ channels by 5-HT may be important in inhibiting the cerebrospinal fluid secretion and/or increasing K+ absorption by the choroid plexus epithelium.

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