Serotonin and protein kinase C modulation of a rat brain inwardly rectifying K+ channel expressed in xenopus oocytes.
In Xenopus laevis oocytes injected with rat brain poly(A)+ RNA, perfusion with a high-K+ solution (96 mM KCl) generated an inward current (IHK) which was absent in water-injected oocytes. Part of IHK was blocked by low concentrations of Ba2+ (half-maximal inhibitory concentration, IC50: 4.2 +/- 0.5 microM). When serotonin (5-HT) was applied to these oocytes a transient inward oscillating Cl- current arising from activation of Ca2+ -dependent Cl- channels, ICl (Ca), was observed. When this response decayed, a 30% reduction of IHK could be detected. Electrophysiological characterization of the K+ channel down-modulated by 5-HT revealed that it is an inward rectifier. Anti-sense suppression experiments revealed that the 5-HT2C receptor mediates the down-modulatory effect of 5-HT. The nature of the modulatory pathway was investigated by application of phorbol esters and intracellular injection of protein kinase C (PKC) inhibitors, ethylenebis (oxonitrilo)tetraacetate (EGTA) and inositol 1,4,5-trisphosphate. The results demonstrate that PKC is responsible for the down-modulatory effect.
DiMagno
L
L
Division of Biology, California Institute of Technology, Pasadena CA 91125, USA.
Dascal
N
N
Davidson
N
N
Lester
H A
HA
Schreibmayer
W
W
D000818:Animals; D001464:Barium / Q000502:physiology; D001483:Base Sequence; D001921:Brain / Q000187:drug effects*; D015536:Down-Regulation; D005260:Female; D008969:Molecular Sequence Data; D009865:Oocytes / Q000737:chemistry / Q000502:physiology*; D015221:Potassium Channels / Q000096:biosynthesis* / Q000187:drug effects / Q000502:physiology*; D051381:Rats; D044405:Receptor, Serotonin, 5-HT2C; D011985:Receptors, Serotonin / Q000502:physiology; D012701:Serotonin / Q000494:pharmacology; D014982:Xenopus laevis
D015221:Potassium Channels; D044405:Receptor, Serotonin, 5-HT2C; D011985:Receptors, Serotonin; D001464:Barium; D012701:Serotonin