Whole-cell recordings of inwardly rectifying K+ currents activated by 5-HT1A receptors on dorsal raphe neurones of the adult rat

J Physiol. 1993 Sep;469:387-405. doi: 10.1113/jphysiol.1993.sp019819.

Abstract

1. An inwardly rectifying K+ current activated by serotonin (5-HT) was recorded from acutely isolated adult dorsal raphe (DR) neurones using the whole-cell recording mode of the patch clamp technique. 2. The 5-HT-induced K+ current (I5-HT) was only visible at an [K+]0 > 5 mM and it was observed in 69% of the cells. 3. The reversal potential for I5-HT was close to the potassium equilibrium potential and was shifted by 51 mV per 10-fold change in [K+]0 indicating that I5-HT was carried predominantly by K+. The chord conductance of I5-HT at -90 mV was proportional to the external [K+] raised to a fractional power. 4. A dose-response relationship revealed that I5-HT was activated with an ED50 of 30 nM. Ba2+ (0.1 mM) blocked I5-HT completely. Spiperone reversibly antagonized the response to 5-HT and 8-OHDPAT (8-hydroxy-2-(di-n-propylamino)tetralin) mimicked the response indicating that the receptor activated was of the 5-HT1A subtype. 5. The response to 5-HT was largely prevented by in vitro pretreatment of the cells with pertussis toxin (PTX) indicating the involvement of a PTX-sensitive G-protein in the transduction mechanism. 6. cAMP and lipoxygenase metabolites, both implicated in the modulation of similar currents in other preparations, were found not to alter the effectiveness of 5-HT. 7. Glibenclamide and tolbutamide, blockers of the ATP-regulated K+ channel, did not reduce the effect of 5-HT in DR neurones. 8. These results show that in acutely isolated adult DR neurones 5-HT activates an inwardly rectifying K+ current and this involves a PTX-sensitive G-protein in the transduction pathway which may interact with the K+ channel directly.

Publication types

  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • 8-Hydroxy-2-(di-n-propylamino)tetralin / pharmacology
  • Animals
  • Barium / pharmacology
  • Cyclic AMP / pharmacology
  • Electrophysiology
  • Glyburide / pharmacology
  • In Vitro Techniques
  • Ion Channel Gating / drug effects
  • Masoprocol / pharmacology
  • Membrane Potentials / drug effects
  • Neurons / drug effects
  • Neurons / metabolism*
  • Pertussis Toxin
  • Potassium / pharmacology
  • Potassium Channels / drug effects*
  • Raphe Nuclei / cytology
  • Raphe Nuclei / drug effects
  • Raphe Nuclei / metabolism*
  • Rats
  • Receptors, Serotonin / drug effects*
  • Receptors, Serotonin / metabolism
  • Serotonin / metabolism
  • Serotonin / physiology
  • Serotonin Antagonists / pharmacology
  • Spiperone / pharmacology
  • Tolbutamide / pharmacology
  • Virulence Factors, Bordetella / pharmacology

Substances

  • Potassium Channels
  • Receptors, Serotonin
  • Serotonin Antagonists
  • Virulence Factors, Bordetella
  • Barium
  • Serotonin
  • Spiperone
  • 8-Hydroxy-2-(di-n-propylamino)tetralin
  • Masoprocol
  • Tolbutamide
  • Cyclic AMP
  • Pertussis Toxin
  • Potassium
  • Glyburide