title: Characterization of the K+ current mediated by 5-HT1A receptor in the acutely dissociated rat dorsal raphe neurons.
abstract: 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.
authors.affiliation: Research Laboratories, Yoshitomi Pharmaceutical Industries, Ltd., Fukuoka, Japan.
authors.forename: J
authors.initials: J
authors.lastname: Katayama
authors.forename: T
authors.initials: T
authors.lastname: Yakushiji
authors.forename: N
authors.initials: N
authors.lastname: Akaike
mesh_terms: D000818:Animals; D002118:Calcium / Q000502:physiology; D004594:Electrophysiology; D004791:Enzyme Inhibitors / Q000494:pharmacology; D005033:Ethylmaleimide / Q000494:pharmacology; D006150:Guanine Nucleotides / Q000494:pharmacology; D066298:In Vitro Techniques; D008564:Membrane Potentials / Q000187:drug effects / Q000502:physiology; D009474:Neurons / Q000502:physiology*; D018408:Patch-Clamp Techniques; D015221:Potassium Channels / Q000187:drug effects / Q000378:metabolism*; D011493:Protein Kinase C / Q000037:antagonists & inhibitors / Q000502:physiology; D011903:Raphe Nuclei / Q000166:cytology / Q000502:physiology*; D051381:Rats; D017208:Rats, Wistar; D011985:Receptors, Serotonin / Q000502:physiology*; D012701:Serotonin / Q000494:pharmacology; D012702:Serotonin Antagonists / Q000494:pharmacology; D017366:Serotonin Receptor Agonists / Q000494:pharmacology
chemical_list: D004791:Enzyme Inhibitors; D006150:Guanine Nucleotides; D015221:Potassium Channels; D011985:Receptors, Serotonin; D012702:Serotonin Antagonists; D017366:Serotonin Receptor Agonists; D012701:Serotonin; D011493:Protein Kinase C; D005033:Ethylmaleimide; D002118:Calcium