G alpha o1 decapeptide modulates the hippocampal 5-HT1A potassium current.
1. The serotonin1A (5-HT1A) receptor is coupled to an inwardly rectifying potassium current (IKir) 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 Go1 and Gi2 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 IKir, which was blocked by the selective 5-HT1A receptor antagonist, pindobind5-HT1A. The G alpha o1 peptide inhibited the 5-HT1A IKir 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 IKir in hippocampal granule cells. They also suggest that G alpha o1 occludes the 5-HT1A response by direct activation of the IKir. 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.
Oleskevich
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Division of Neuroscience, John Curtin School of Medical Research, Australian National University, Canberra, Australia.
D000818:Animals; D019204:GTP-Binding Proteins / Q000737:chemistry*; D006624:Hippocampus / Q000502:physiology*; D066298:In Vitro Techniques; D009842:Oligopeptides / Q000502:physiology*; D015221:Potassium Channels / Q000502:physiology*; D051381:Rats; D017208:Rats, Wistar; D011985:Receptors, Serotonin / Q000502:physiology*
D009842:Oligopeptides; D015221:Potassium Channels; D011985:Receptors, Serotonin; D019204:GTP-Binding Proteins