G(ALPHA-O1) DECAPEPTIDE MODULATES THE HIPPOCAMPAL 5-HT1A POTASSIUM CURRENT

1. The serotonin(1A) (5-HT1A) receptor is coupled to an inwardly rectifying potassium current (I-Kir) via a G protein. The identity of the G-protein subtype was investigated with 2 10-amino acid peptides derived from the carboxyl (C) terminus of the alpha-subunits of the G(o1) and G(i2) proteins (G(alpha o1) and G(alpha i2)) The synthetic decapeptides were applied by intracellular perfusion during whole cell recording from dentate granule cells in the hippocampal slice preparation. 2. Bath application of 5-HT produced an I-Kir, which was blocked by the selective 5-HT1A receptor antagonist, pindobind5-HT1A. The G(alpha o1) peptide inhibited the 5-HT1A I-Kir by 60 +/- 7% (mean +/- SE; t = 30 min), whereas the G(alpha i2) peptide had no effect. The G(alpha o1) peptide produced a slowly developing outward current that was not observed in the absence of peptide or in the presence of the G(alpha i2) peptide. 3. The results indicate that G(alpha o1) and not G(alpha i2) modulates the 5-HT1A I-Kir in hippocampal granule cells. They also suggest that G(alpha o1) occludes the 5-HT1A response by direct activation of the I-Kir. The intracellular perfusion of synthetic G(alpha) peptides provides a new approach to identify the G-protein subtype(s) in a receptor-mediated electrophysiological response.