K+ channel and 5-hydroxytryptamine1A autoreceptor interactions in the rat dorsal raphe nucleus: an in vitro electrophysiological study.
Extracellular recordings were made from serotonergic neurons of the rat dorsal raphe nucleus in a slice preparation. In the presence of phenylephrine (3 microM) to restore the pacemaker activity of otherwise silent serotonergic neurons, superfusion with the 5-hydroxytryptamine1A agonist ipsapirone depressed the firing of these neurons with an IC50 of approximately 50 nM. Complete inhibition was achieved with 100-300 nM of the drug. Concomitant superfusion with the 5-hydroxytryptamine1A antagonists spiperone (100 nM) or propranolol (10 microM) markedly reduced the inhibitory effect of ipsapirone (100 nM). Superfusion with K+ channel blockers such as apamin (50-100 nM), charybdotoxin (100 nM) or Ba2+ (1 mM) did not induce any changes in the electrical activity of serotonergic neurons. However, 4-aminopyridine (0.1-1 mM) disrupted the regularity of their discharge without affecting the mean firing rate. The ipsapirone-induced inhibition was unchanged by apamin and charybdotoxin, but was markedly reduced by Ba2+ and 4-aminopyridine. Thus the IC50 of ipsapirone was shifted to approximately 150 nM in the presence of 1 mM of 4-aminopyridine. These results indicate that, in serotonergic neurons within the dorsal raphe nucleus, the K+ channel opened through the stimulation of 5-hydroxytryptamine1A autoreceptors is 4-aminopyridine-sensitive.
Haj-Dahmane
S
S
INSERM U.288, Faculté de Médecine Pitié-Salpêtrière, Paris, France.
Hamon
M
M
Lanfumey
L
L
D015761:4-Aminopyridine / Q000494:pharmacology; D000818:Animals; D014151:Anti-Anxiety Agents; D001030:Apamin / Q000494:pharmacology; D001464:Barium / Q000494:pharmacology; D018999:Charybdotoxin; D004594:Electrophysiology / Q000379:methods; D005071:Evoked Potentials / Q000187:drug effects; D008297:Male; D009474:Neurons / Q000187:drug effects / Q000502:physiology*; D010656:Phenylephrine / Q000494:pharmacology; D015221:Potassium Channels / Q000187:drug effects / Q000502:physiology*; D011433:Propranolol / Q000494:pharmacology; D011743:Pyrimidines / Q000494:pharmacology; D011903:Raphe Nuclei / Q000187:drug effects / Q000502:physiology*; D051381:Rats; D011919:Rats, Inbred Strains; D011985:Receptors, Serotonin / Q000187:drug effects / Q000502:physiology*; D012604:Scorpion Venoms / Q000494:pharmacology; D013134:Spiperone / Q000494:pharmacology
D014151:Anti-Anxiety Agents; D015221:Potassium Channels; D011743:Pyrimidines; D011985:Receptors, Serotonin; D012604:Scorpion Venoms; D018999:Charybdotoxin; D010656:Phenylephrine; D001030:Apamin; D001464:Barium; D013134:Spiperone; C043077:ipsapirone; D011433:Propranolol; D015761:4-Aminopyridine