title: Inactivation of GIRK channels weakens the pre- and postsynaptic inhibitory activity in dorsal raphe neurons.
abstract: The serotonergic tone of the dorsal raphe (DR) is regulated by 5-HT1Areceptors, which negatively control serotonergic activity via the activation of G protein-coupled inwardly rectifying K+(GIRK) channels. In addition, DR activity is modulated by local GABAergic transmission, which is believed to play a key role in the development of mood-related disorders. Here, we sought to characterize the role of GIRK2 subunit-containing channels on the basal electrophysiological properties of DR neurons and to investigate whether the presynaptic and postsynaptic activities of 5-HT1A, GABAB, and GABAAreceptors are affected byGirk2gene deletion. Whole-cell patch-clamp recordings in brain slices from GIRK2 knockout mice revealed that the GIRK2 subunit contributes to maintenance of the resting membrane potential and to the membrane input resistance of DR neurons. 5-HT1Aand GABABreceptor-mediated postsynaptic currents were almost absent in the mutant mice. Spontaneous and evoked GABAAreceptor-mediated transmissions were markedly reduced in GIRK2 KO mice, as the frequency and amplitude of spontaneous IPSCs were reduced, the paired-pulse ratio was increased and GABA-induced whole-cell currents were decreased. Similarly, the pharmacological blockade of GIRK channels with tertiapin-Q prevented the 5-HT1Aand GABABreceptor-mediated postsynaptic currents and increased the paired-pulse ratio. Finally, deletion of theGirk2gene also limited the presynaptic inhibition of GABA release exerted by 5-HT1Aand GABABreceptors. These results indicate that the properties and inhibitory activity of DR neurons are highly regulated by GIRK2 subunit-containing channels, introducing GIRK channels as potential candidates for studying the pathophysiology and treatment of affective disorders.
authors.affiliation: Department of Pharmacology, Faculty of Medicine and Nursing, University of the Basque Country UPV/EHU, Leioa, Spain.
authors.forename: Nerea
authors.initials: N
authors.lastname: Llamosas
authors.affiliation: Department of Pharmacology, Faculty of Medicine and Nursing, University of the Basque Country UPV/EHU, Leioa, Spain.
authors.forename: Luisa
authors.initials: L
authors.lastname: Ugedo
authors.affiliation: Department of Pharmacology, Faculty of Medicine and Nursing, University of the Basque Country UPV/EHU, Leioa, Spain maria.torrecilla@ehu.eus.
authors.forename: Maria
authors.initials: M
authors.lastname: Torrecilla
mesh_terms: D000200:Action Potentials; D000818:Animals; D065847:Dorsal Raphe Nucleus / Q000502:physiology*; D051676:G Protein-Coupled Inwardly-Rectifying Potassium Channels / Q000502:physiology*; D053444:Inhibitory Postsynaptic Potentials; D051379:Mice; D018345:Mice, Knockout; D009474:Neurons / Q000502:physiology*; D021122:Protein Subunits; D044282:Receptor, Serotonin, 5-HT1A / Q000502:physiology; D011963:Receptors, GABA-A / Q000502:physiology; D018080:Receptors, GABA-B / Q000502:physiology; D013569:Synapses / Q000502:physiology*; D005680:gamma-Aminobutyric Acid / Q000378:metabolism
chemical_list: D051676:G Protein-Coupled Inwardly-Rectifying Potassium Channels; C497069:Kcnj6 protein, mouse; D021122:Protein Subunits; D011963:Receptors, GABA-A; D018080:Receptors, GABA-B; D044282:Receptor, Serotonin, 5-HT1A; D005680:gamma-Aminobutyric Acid
keywords: 
  GABA
  ; 
  GIRK
  ; 
  IPSC
  ; Depression; dorsal raphe