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Serotonin and protein kinase C modulation of a rat brain inwardly rectifying K+ channel expressed inXenopus oocytes

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Abstract

InXenopus laevis oocytes injected with rat brain poly(A)+ RNA, perfusion with a high-K+ solution (96 mM KCl) generated an inward current (I HK) which was absent in water-injected oocytes. Part ofI HK was blocked by low concentrations of Ba2+ (half-maximal inhibitory concentration, IC50: 4.2 ± 0.5 μM). When serotonin (5-HT) was applied to these oocytes a transient inward oscillating Cl− current arising from activation of Ca2+ -dependent Cl− channels,I Cl(Ca), was observed. When this response decayed, a 30% reduction ofI HK could be detected. Electrophysiological characterization of the K+ channel down-modulated by 5-HT revealed that it is an inward rectifier. Antisense 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.

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Authors and Affiliations

  1. Division of Biology, California Institute of Technology, 91125, Pasadena, CA, USA

    Lisa DiMagno, Norman Davidson & Henry A. Lester

  2. Department of Physiology and Pharmacology, Sackler Medical School, Tel Aviv University, 69978, Ramat Aviv, Israel

    Nathan Dascal

  3. Institute of Medical Physics and Biophysics, University of Graz, Harrachgasse 21/IV, A-8010, Graz, Austria

    Wolfgang Schreibmayer

Authors
  1. Lisa DiMagno
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  2. Nathan Dascal
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  3. Norman Davidson
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  4. Henry A. Lester
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  5. Wolfgang Schreibmayer
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DiMagno, L., Dascal, N., Davidson, N. et al. Serotonin and protein kinase C modulation of a rat brain inwardly rectifying K+ channel expressed inXenopus oocytes. Pflugers Arch. 431, 335–340 (1996). https://doi.org/10.1007/BF02207270

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  • DOI: https://doi.org/10.1007/BF02207270

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