Whole-cell recordings of inwardly rectifying K+ currents activated by 5-HT1A receptors on dorsal raphe neurones of the adult rat.
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.
Penington
N J
NJ
Department of Pharmacological and Physiological Sciences, University of Chicago, IL 60637.
Kelly
J S
JS
Fox
A P
AP
D017371:8-Hydroxy-2-(di-n-propylamino)tetralin / Q000494:pharmacology; D000818:Animals; D001464:Barium / Q000494:pharmacology; D000242:Cyclic AMP / Q000494:pharmacology; D004594:Electrophysiology; D005905:Glyburide / Q000494:pharmacology; D066298:In Vitro Techniques; D015640:Ion Channel Gating / Q000187:drug effects; D009637:Masoprocol / Q000494:pharmacology; D008564:Membrane Potentials / Q000187:drug effects; D009474:Neurons / Q000187:drug effects / Q000378:metabolism*; D037342:Pertussis Toxin; D011188:Potassium / Q000494:pharmacology; D015221:Potassium Channels / Q000187:drug effects*; D011903:Raphe Nuclei / Q000166:cytology / Q000187:drug effects / Q000378:metabolism*; D051381:Rats; D011985:Receptors, Serotonin / Q000187:drug effects* / Q000378:metabolism; D012701:Serotonin / Q000378:metabolism / Q000502:physiology; D012702:Serotonin Antagonists / Q000494:pharmacology; D013134:Spiperone / Q000494:pharmacology; D014044:Tolbutamide / Q000494:pharmacology; D010566:Virulence Factors, Bordetella / Q000494:pharmacology
D015221:Potassium Channels; D011985:Receptors, Serotonin; D012702:Serotonin Antagonists; D010566:Virulence Factors, Bordetella; D001464:Barium; D012701:Serotonin; D013134:Spiperone; D017371:8-Hydroxy-2-(di-n-propylamino)tetralin; D009637:Masoprocol; D014044:Tolbutamide; D000242:Cyclic AMP; D037342:Pertussis Toxin; D011188:Potassium; D005905:Glyburide