RT Journal Article
T1 Subcellular compartment-specific molecular diversity of pre- and post-synaptic GABA-activated GIRK channels in Purkinje cells
A1 Fernández-Alacid, Laura
A1 Aguado, Carolina
A1 Ciruela, Francisco
A1 Martín Herranz, Ricardo
A1 Colón, José
A1 Cabañero, María José
A1 Gassman, Martin
A1 Watanabe, Masahiko
A1 Shigemoto, Ryuichi
A1 Wickman, Kevin
A1 Bettler, Bernhard
A1 Sánchez-Prieto Borja, José
A1 Luján, Rafael
AB Activation of G protein-gated inwardly-rectifying K+ (GIRK or Kir3) channels by metabotropic gamma-aminobutyric acid (B) (GABAB) receptors is an essential signalling pathway controlling neuronal excitability and synaptic transmission in the brain. To investigate the relationship between GIRK channel subunits and GABAB receptors in cerebellar Purkinje cells at post- and pre-synaptic sites, we used biochemical, functional and immunohistochemical techniques. Co-immunoprecipitation analysis demonstrated that GIRK subunits are co-assembled with GABAB receptors in the cerebellum. Immunoelectron microscopy showed that the subunit composition of GIRK channels in Purkinje cell spines is compartment-dependent. Thus, at extrasynaptic sites GIRK channels are formed by GIRK1/GIRK2/GIRK3, post-synaptic densities contain GIRK2/GIRK3 and dendritic shafts contain GIRK1/GIRK3. The post-synaptic association of GIRK subunits with GABAB receptors in Purkinje cells is supported by the subcellular regulation of the ion channel and the receptor in mutant mice. At pre-synaptic sites, GIRK channels localized to parallel fibre terminals are formed by GIRK1/GIRK2/GIRK3 and co-localize with GABAB receptors. Consistent with this morphological evidence we demonstrate their functional interaction at axon terminals in the cerebellum by showing that GIRK channels play a role in the inhibition of glutamate release by GABAB receptors. The association of GIRK channels and GABA B receptors with excitatory synapses at both post- and pre-synaptic sites indicates their intimate involvement in the modulation of glutamatergic neurotransmission in the cerebellum.
PB Wiley
SN 1471-4159
YR 2009
FD 2009
LK https://hdl.handle.net/20.500.14352/98013
UL https://hdl.handle.net/20.500.14352/98013
LA eng
NO Fernández‐Alacid, Laura, et al. «Subcellular Compartment‐specific Molecular Diversity of Pre‐ and Post‐synaptic GABAB ‐activated GIRK Channels in Purkinje Cells». Journal of Neurochemistry, vol. 110, n.o 4, agosto de 2009, pp. 1363-76. https://doi.org/10.1111/j.1471-4159.2009.06229.x.
NO National Institute of Neurological Disorders and Stroke
NO Ministerio de Educación y Ciencia (España)
NO Ministerio de Ciencia e Innovación (España) 
NO Instituto de Salud Carlos III
NO Comunidad de Madrid
DS Docta Complutense
RD 17 dic 2025