TANDOSPIRONE-INDUCED K+ CURRENT IN ACUTELY DISSOCIATED RAT DORSAL RAPHE NEURONS

1 The effects of tandospirone (TDS) on dissociated rat dorsal raphe ne urones were investigated using the patch-clamp method. 2 Under current -clamp conditions, TDS hyperpolarized the cell membrane, resulting in the reduction of firing rates. 3 Under voltage-clamp conditions, TDS i nduced an inward rectifying K+ current in a concentration-dependent ma nner. 4 The TDS-induced K+ currents (I-TDS) were mimicked by 8-OH-DPAT , a 5-HT1A agonist. The I-TDS was blocked by spiperone, a 5-HT1A recep tor antagonist, in a concentration-dependent manner. 5 N-Ethylmaleimid e, an agent which uncouples between the receptor and the G-protein, ir reversibly blocked the ITDS 6 In neurones perfused intracellularly wit h a pipette-solution containing GTP using the conventional whole-cell patch recording, the I-TDS showed a gradual rundown. When the neurones were perfused with GTP gamma S, TDS activated the inwardly rectifying K+ current in an irreversible manner. 7 In the inside-out patch recor ding mode, TDS-activated single K+ channel currents (i(TDS)) which als o showed an inward rectification. When the GDP in cytosolic side was c ompletely replaced with GTP, the open probability of i(TDS) significan tly increased. 8 These results indicate that the activation of 5-HT1A receptors by TDS directly opens the inward rectifying K+ channels via a G-protein mediated process.