Whole‐cell recordings of inwardly rectifying K+ currents activated by 5‐HT1A receptors on dorsal raphe neurones of the adult rat.

Abstract

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. © 1993 The Physiological Society