Characterization of the K+ current mediated by 5-HT1A receptor in the acutely dissociated rat dorsal raphe neurons

Brain Res. 1997 Jan 16;745(1-2):283-92. doi: 10.1016/s0006-8993(96)01141-9.


The action of 5-hydroxytryptamine (5-HT) via the 5-HT1A receptor on dissociated rat dorsal raphe neurons was characterized under the whole-cell mode by using the nystatin-perforated patch-clamp technique. Under voltage-clamp conditions, 5-HT induced an inwardly rectifying K+ current (I5-HT) in a concentration-dependent manner. I5-HT was mimicked by 8-OH-DPAT and buspirone, which are both 5-HT1A receptor agonists. I5-HT was reversibly blocked by such 5-HT1A receptor antagonists as (S)-UH-301 a 5-HT4 receptor antagonist. I5-HT was antagonized concentration-dependently by such K+ channel blockers as quinine, Ba2+ and 4-aminopyridine but was relatively insensitive to both CS+ and tetraethylammonium. When the neurons were loaded with guanosine 5'-O-3-thiotriphosphate through a patch pipette, the K+ current induced by 5-HT became irreversible. N-ethylmaleimide (NEM), a sulfhydryl alkylating agent, irreversibly blocked I5-HT. The intracellular perfusion with 1,2-bis(2-aminophenoxy)ethane-N,N,N',N'-tetraacetic acid (BAPTA), a Ca2+ chelator, or neomycine, a phospholipase C inhibitor, never significantly affected the 5-HT-induced response. 12-Myristate 13-acetate diester (PMA), a protein kinase C (PKC) activator, had only a weak inhibitory effect on I5-HT, and staurosporine, a PKC inhibitor, failed to significantly occlude I5-HT. Therefore, the K+ conductance activated via the 5-HT1a receptor of dorsal raphe neurons was thus characterized by the sensitivity to such K+ channel blockers as quinine, Ba2+ and 4-aminopyridine. Moreover, G protein which is NEM-sensitive and can couple to the 5-HT1A receptor, is thus considered to activate the inwardly rectifying K+ conductance without being mediated by such second messengers as Ca2+ and PKC.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Calcium / physiology
  • Electrophysiology
  • Enzyme Inhibitors / pharmacology
  • Ethylmaleimide / pharmacology
  • Guanine Nucleotides / pharmacology
  • In Vitro Techniques
  • Membrane Potentials / drug effects
  • Membrane Potentials / physiology
  • Neurons / physiology*
  • Patch-Clamp Techniques
  • Potassium Channels / drug effects
  • Potassium Channels / metabolism*
  • Protein Kinase C / antagonists & inhibitors
  • Protein Kinase C / physiology
  • Raphe Nuclei / cytology
  • Raphe Nuclei / physiology*
  • Rats
  • Rats, Wistar
  • Receptors, Serotonin / physiology*
  • Serotonin / pharmacology
  • Serotonin Antagonists / pharmacology
  • Serotonin Receptor Agonists / pharmacology


  • Enzyme Inhibitors
  • Guanine Nucleotides
  • Potassium Channels
  • Receptors, Serotonin
  • Serotonin Antagonists
  • Serotonin Receptor Agonists
  • Serotonin
  • Protein Kinase C
  • Ethylmaleimide
  • Calcium