WHOLE-CELL RECORDINGS OF INWARDLY RECTIFYING K-HT(1A) RECEPTORS ON DORSAL RAPHE NEURONS OF THE ADULT-RAT( CURRENTS ACTIVATED BY 5)

1. An inwardly rectifying K+ current activated by ser tonin (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+]o > 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+]o indicating that I5-HT was carried p redominantly by K+. The chord conductance of I5-HT at -90 mV was propo rtional to the external [K+] raised to a fractional power. 4. A dose-r esponse relationship revealed that I5-HT was activated with an ED50 of 30 nm. Ba2+ (0.1 mM) blocked I5-HT completely. Spiperone reversibly a ntagonized the response to 5-HT and 8-OHDPAT (8-hydroxy-2-(di-n-propyl amino)tetralin) mimicked the response indicating that the receptor act ivated 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 tr ansduction mechanism. 6. cAMP and lipoxygenase metabolites, both impli cated in the modulation of similar currents in other preparations, wer e found not to alter the effectiveness of 5-HT. 7. Glibenclamide and t olbutamide, blockers of the ATP-regulated K+ channel, did not reduce t he effect of 5-HT in DR neurones. 8. These results show that in acutel y isolated adult DR neurones 5-HT activates an inwardly rectifying Kcurrent and this involves a PTX-sensitive G-protein in the transductio n pathway which may interact with the K+ channel directly.