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Subcellular compartment‐specific molecular diversity of pre‐ and post‐synaptic GABA B ‐activated GIRK channels in Purkinje cells
Author(s) -
FernándezAlacid Laura,
Aguado Carolina,
Ciruela Francisco,
Martín Ricardo,
Colón José,
Cabañero María José,
Gassmann Martin,
Watanabe Masahiko,
Shigemoto Ryuichi,
Wickman Kevin,
Bettler Bernhard,
SánchezPrieto José,
Luján Rafael
Publication year - 2009
Publication title -
journal of neurochemistry
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.75
H-Index - 229
eISSN - 1471-4159
pISSN - 0022-3042
DOI - 10.1111/j.1471-4159.2009.06229.x
Subject(s) - g protein coupled inwardly rectifying potassium channel , neuroscience , neurotransmission , metabotropic receptor , excitatory postsynaptic potential , glutamate receptor , biology , cerebellum , gabab receptor , purkinje cell , glutamatergic , microbiology and biotechnology , chemistry , inhibitory postsynaptic potential , receptor , gabaa receptor , g protein , biochemistry , signal transduction
Activation of G protein‐gated inwardly‐rectifying K + (GIRK or Kir3) channels by metabotropic gamma‐aminobutyric acid (B) (GABA B ) receptors is an essential signalling pathway controlling neuronal excitability and synaptic transmission in the brain. To investigate the relationship between GIRK channel subunits and GABA B 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 GABA B 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 GABA B 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 GABA B 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 GABA B 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.