title: Intracellular chloride concentration influences the GABAA receptor subunit composition.
abstract: GABA(A) receptors (GABA(A)Rs) exist as different subtype variants showing unique functional properties and defined spatio-temporal expression pattern. The molecular mechanisms underlying the developmental expression of different GABA(A)R are largely unknown. The intracellular concentration of chloride ([Cl(-)](i)), the main ion permeating through GABA(A)Rs, also undergoes considerable changes during maturation, being higher at early neuronal stages with respect to adult neurons. Here we investigate the possibility that [Cl(-)](i) could modulate the sequential expression of specific GABA(A)Rs subtypes in primary cerebellar neurons. We show that [Cl(-)](i) regulates the expression of α3-1 and δ-containing GABA(A) receptors, responsible for phasic and tonic inhibition, respectively. Our findings highlight the role of [Cl(-)](i) in tuning the strength of GABAergic responses by acting as an intracellular messenger.
authors.affiliation: Department of Neuroscience and Brain Technologies, The Italian Institute of Technology, Genova 16163, Italy.
authors.forename: Francesca
authors.initials: F
authors.lastname: Succol
authors.forename: Hubert
authors.initials: H
authors.lastname: Fiumelli
authors.forename: Fabio
authors.initials: F
authors.lastname: Benfenati
authors.forename: Laura
authors.initials: L
authors.lastname: Cancedda
authors.forename: Andrea
authors.initials: A
authors.lastname: Barberis
mesh_terms: D000818:Animals; D002034:Bumetanide / Q000494:pharmacology; D002264:Carboxylic Acids / Q000494:pharmacology; D002478:Cells, Cultured; D002531:Cerebellum / Q000737:chemistry / Q000166:cytology; D002712:Chlorides / Q000032:analysis / Q000378:metabolism*; D007192:Indenes / Q000494:pharmacology; D007555:Isoxazoles; D051379:Mice; D009474:Neurons / Q000737:chemistry / Q000166:cytology / Q000378:metabolism*; D018408:Patch-Clamp Techniques; D021122:Protein Subunits / Q000378:metabolism; D011725:Pyridines / Q000494:pharmacology; D034622:RNA Interference; D034741:RNA, Small Interfering; D011963:Receptors, GABA-A / Q000737:chemistry* / Q000378:metabolism*; D027981:Symporters / Q000235:genetics / Q000378:metabolism; D000077334:Zolpidem; D005680:gamma-Aminobutyric Acid / Q000378:metabolism; D000096922:K Cl- Cotransporters
chemical_list: D002034:Bumetanide; D002264:Carboxylic Acids; D002712:Chlorides; D007192:Indenes; D007555:Isoxazoles; D021122:Protein Subunits; D011725:Pyridines; D034741:RNA, Small Interfering; D011963:Receptors, GABA-A; D027981:Symporters; D000077334:Zolpidem; D005680:gamma-Aminobutyric Acid; D000096922:K Cl- Cotransporters; C059990:((dihydroindenyl)oxy)alkanoic acid; C015542:gaboxadol