title: Hyperpolarizing GABAergic transmission depends on KCC2 function and membrane potential.
abstract: KCC2 comprises the major Cl(-) extruding mechanism in most adult neurons. Hyperpolarizing GABAergic transmission depends on KCC2 function. We recently demonstrated that glutamate reduces KCC2 function by a phosphorylation-dependent mechanism that leads to excitatory GABA responses. Here we investigated the methods by which to estimate changes in E(GABA), as well as the processes that lead to depolarizing GABA responses and their effects on neuronal excitability. We demonstrated that current-clamp recordings of membrane potential responses to GABA can determine upper and lower limits of E(GABA). We also further characterized depolarizing GABA responses, which both excited and inhibited neurons. Our analyses revealed that persistently active GABA(A) receptors contributed to loading Cl(-) during the glutamate exposure, indicating that tonic inhibition can facilitate the development of depolarizing GABA responses and increase excitability after pathophysiological insults. Finally, we demonstrated that hyperpolarizing GABA responses could temporarily switch to depolarizing responses when they coincided with an afterhyperpolarization.
authors.affiliation: Tufts University, Boston, MA, USA.
authors.forename: Tarek Z
authors.initials: TZ
authors.lastname: Deeb
authors.forename: Henry H C
authors.initials: HH
authors.lastname: Lee
authors.forename: Joshua A
authors.initials: JA
authors.lastname: Walker
authors.forename: Paul A
authors.initials: PA
authors.lastname: Davies
authors.forename: Stephen J
authors.initials: SJ
authors.lastname: Moss
mesh_terms: D002712:Chlorides / Q000378:metabolism; D059330:GABAergic Neurons / Q000378:metabolism*; D006801:Humans; D017136:Ion Transport / Q000502:physiology; D008564:Membrane Potentials / Q000502:physiology*; D011963:Receptors, GABA-A / Q000378:metabolism*; D027981:Symporters / Q000378:metabolism*; D009435:Synaptic Transmission / Q000502:physiology*; D005680:gamma-Aminobutyric Acid / Q000378:metabolism*; D000096922:K Cl- Cotransporters
chemical_list: D002712:Chlorides; D011963:Receptors, GABA-A; D027981:Symporters; D005680:gamma-Aminobutyric Acid; D000096922:K Cl- Cotransporters
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