Altered presynaptic and postsynaptic transmission in Dorsal Raphe neurons of GIRK2 knockout mice

Llamosas, N. , Ugedo, L. & María, T.

Department of Pharmacology, Faculty of Medicine and Dentistry, University of the Basque Country, Leioa, Vizcaya, Spain.

We examined the involvement of G-protein-coupled inwardly rectifying potassium (GIRK) channels in 5-HT, GABAergic and glutamatergic synaptic activity in Dorsal Raphe (DR) neurons of mice lacking Girk2 gene. Thus, whole-cell patch-clamp experiments were performed in DR slices examining outward currents evoked by 5-HT1A (5-CT) and GABAB receptors (baclofen) agonists, as well as the spontaneous and evoked excitatory and inhibitory postsynaptic currents.
In wild-type mice, 5-CT and baclofen elicited outward currents that were largely diminished in GIRK2 knockout mice. Regarding presynaptic GABA release, the frequency and amplitude of sIPSC were significantly decreased and the number of neurons which showed paired-pulse facilitation of eIPSC was significantly greater in DR of GIRK2 knockout mice. Then, we investigated whether this difference in GABA release was due to an altered 5-HT transmission. The 5-HT1A antagonist, WAY100635 produced an increase in the frequency of sIPSC in wild-type mice that was significantly smaller in GIRK2 knockout group. Presynaptic release of glutamate remained unaltered in the mutant mice.
This study demonstrates that in DR, GIRK2 channels are the main inhibitory effectors of the postsynaptic actions of 5-HT1A and GABAB receptors. Moreover, Girk2 gene deletion reduces GABA release in DR neurons by affecting 5-HT transmission.
Supported by Saiotek S-PE11UN055, FIS PI12/00613, Basque Government IT747-13 and University of the Basque Country UFI 11/12. N Llamosas has a grant from UPV/EHU.