title: Activity-mediated shift in reversal potential of GABA-ergic synaptic currents in immature neurons.
abstract: Gamma-aminobutyric acid (GABA), which is inhibitory in the adult central nervous system, can be excitatory in the developing brain. The change from excitatory to inhibitory action of GABA during development is caused by a negative shift in its reversal potential. Here, we report a presynaptic activity-mediated negative shift in the reversal potential of the GABA-mediated synaptic currents in immature deep cerebellar nuclei neurons. This shift appears to be due to an increased expression and activation of the K+-Cl- co-transporter type 2 (KCC-2) through the activation of protein kinase A, protein synthesis and activation of protein phosphatases. Thus, maturation of the GABA response may rely on an activity-dependent up-regulation of KCC-2.
authors.affiliation: Neuroscience Research Laboratory, Department of Pharmacology and Therapeutics, The University of British Columbia, Faculty of Medicine, 2176 Health Sciences Mall, Vancouver, BC, Canada V6T 1Z3.
authors.forename: M
authors.initials: M
authors.lastname: Ouardouz
authors.forename: B R
authors.initials: BR
authors.lastname: Sastry
mesh_terms: D000818:Animals; D000831:Animals, Newborn; D002454:Cell Differentiation / Q000235:genetics; D002529:Cerebellar Nuclei / Q000254:growth & development / Q000378:metabolism; D018118:Chloride Channels / Q000187:drug effects / Q000378:metabolism; D017868:Cyclic AMP-Dependent Protein Kinases / Q000378:metabolism; D005665:Furosemide / Q000494:pharmacology; D009433:Neural Inhibition / Q000187:drug effects / Q000235:genetics*; D009474:Neurons / Q000187:drug effects / Q000378:metabolism*; D009924:Organ Culture Techniques; D018408:Patch-Clamp Techniques; D010749:Phosphoprotein Phosphatases / Q000378:metabolism; D051381:Rats; D017208:Rats, Wistar; D049994:Sodium Potassium Chloride Symporter Inhibitors / Q000494:pharmacology; D027981:Symporters / Q000037:antagonists & inhibitors / Q000235:genetics / Q000378:metabolism*; D013569:Synapses / Q000187:drug effects / Q000378:metabolism*; D009435:Synaptic Transmission / Q000187:drug effects / Q000235:genetics*; D015854:Up-Regulation / Q000187:drug effects / Q000235:genetics; D005680:gamma-Aminobutyric Acid / Q000378:metabolism*; D000096922:K Cl- Cotransporters
chemical_list: D018118:Chloride Channels; D017868:Cyclic AMP-Dependent Protein Kinases; D005665:Furosemide; D010749:Phosphoprotein Phosphatases; D049994:Sodium Potassium Chloride Symporter Inhibitors; D027981:Symporters; D005680:gamma-Aminobutyric Acid; D000096922:K Cl- Cotransporters