Receptors of the serotonin 1C subtype expressed from cloned DNA mediate the closing of K+ membrane channels encoded by brain mRNA.
The modulation of K+ channels by serotonin (5-HT) receptors was studied by coinjecting Xenopus oocytes with mRNA transcribed in vitro from a cloned 5-HT 1C subtype (5-HT1C) receptor gene, together with size-fractionated mRNA isolated from rat cerebral cortex that expresses K+ channels. After intracellular loading with EGTA to block Ca2(+)-dependent chloride currents, these oocytes responded to 5-HT with an inward current associated with a decrease in membrane conductance. Membrane current responses were small or absent in oocytes injected with either mRNA alone. We conclude that 5-HT1C receptors are able to cause the closing of a class of K+ channels expressed by cortex mRNA in a Ca2(+)-independent manner. The coupling between the receptors and channels appears to be mediated by the inositol phospholipid second messenger pathway, since activation of this pathway by application of serum evoked a similar closing current.
Panicker
M M
MM
Department of Psychobiology, University of California, Irvine 92717.
Parker
I
I
Miledi
R
R
D000818:Animals; D002540:Cerebral Cortex / Q000502:physiology*; D003001:Cloning, Molecular; D005260:Female; D008564:Membrane Potentials / Q000187:drug effects; D008845:Microinjections; D009865:Oocytes / Q000502:physiology*; D015221:Potassium Channels / Q000187:drug effects / Q000235:genetics / Q000502:physiology*; D012333:RNA, Messenger / Q000008:administration & dosage / Q000235:genetics*; D051381:Rats; D011985:Receptors, Serotonin / Q000235:genetics / Q000502:physiology*; D012701:Serotonin / Q000494:pharmacology; D014982:Xenopus laevis
D015221:Potassium Channels; D012333:RNA, Messenger; D011985:Receptors, Serotonin; D012701:Serotonin