title: Cell type-specific subunit composition of G protein-gated potassium channels in the cerebellum.
abstract: G protein-gated inwardly rectifying potassium (GIRK/Kir3) channels regulate cellular excitability and neurotransmission. In this study, we used biochemical and morphological techniques to analyze the cellular and subcellular distributions of GIRK channel subunits, as well as their interactions, in the mouse cerebellum. We found that GIRK1, GIRK2, and GIRK3 subunits co-precipitated with one another in the cerebellum and that GIRK subunit ablation was correlated with reduced expression levels of residual subunits. Using quantitative RT-PCR and immunohistochemical approaches, we found that GIRK subunits exhibit overlapping but distinct expression patterns in various cerebellar neuron subtypes. GIRK1 and GIRK2 exhibited the most widespread and robust labeling in the cerebellum, with labeling particularly prominent in granule cells. A high degree of molecular diversity in the cerebellar GIRK channel repertoire is suggested by labeling seen in less abundant neuron populations, including Purkinje neurons (GIRK1/GIRK2/GIRK3), basket cells (GIRK1/GIRK3), Golgi cells (GIRK2/GIRK4), stellate cells (GIRK3), and unipolar brush cells (GIRK2/GIRK3). Double-labeling immunofluorescence and electron microscopies showed that GIRK subunits were mainly found at post-synaptic sites. Altogether, our data support the existence of rich GIRK molecular and cellular diversity, and provide a necessary framework for functional studies aimed at delineating the contribution of GIRK channels to synaptic inhibition in the cerebellum.
authors: Departamento de Ciencias Médicas, Facultad de Medicina, Universidad de Castilla-La Mancha, Campus Biosanitario, Albacete, Spain.
authors: Carolina
authors: C
authors: Aguado
authors: José
authors: J
authors: Colón
authors: Francisco
authors: F
authors: Ciruela
authors: Falk
authors: F
authors: Schlaudraff
authors: Maria José
authors: MJ
authors: Cabañero
authors: Cydne
authors: C
authors: Perry
authors: Masahiko
authors: M
authors: Watanabe
authors: Birgit
authors: B
authors: Liss
authors: Kevin
authors: K
authors: Wickman
authors: Rafael
authors: R
authors: Luján
mesh_terms: D000818:Animals; D048429:Cell Size; D002531:Cerebellum / Q000166:cytology* / Q000378:metabolism*; D005260:Female; D051676:G Protein-Coupled Inwardly-Rectifying Potassium Channels / Q000172:deficiency / Q000378:metabolism* / Q000648:ultrastructure; D005786:Gene Expression Regulation / Q000235:genetics / Q000502:physiology; D049452:Green Fluorescent Proteins / Q000235:genetics / Q000378:metabolism; D047468:Immunoprecipitation / Q000379:methods; D008297:Male; D051379:Mice; D008822:Mice, Transgenic; D046529:Microscopy, Electron, Transmission / Q000379:methods; D009474:Neurons / Q000145:classification* / Q000378:metabolism* / Q000648:ultrastructure; D021122:Protein Subunits / Q000378:metabolism; D013347:Subcellular Fractions / Q000378:metabolism / Q000648:ultrastructure
chemical_list: D051676:G Protein-Coupled Inwardly-Rectifying Potassium Channels; D021122:Protein Subunits; D049452:Green Fluorescent Proteins