title: Bicarbonate efflux via GABA(A) receptors depolarizes membrane potential and inhibits two-pore domain potassium channels of astrocytes in rat hippocampal slices.
abstract: Increasing evidence indicates the functional expression of ionotropic γ-aminobutyric acid receptor (GABA(A) -R) in astrocytes. However, it remains controversial in regard to the intracellular Cl(-) concentration ([Cl(-) ](i) ) and the functional role of anion-selective GABA(A) -R in astrocytes. In gramicidin perforated-patch recordings from rat hippocampal CA1 astrocytes, GABA and GABA(A) -R-specific agonist THIP depolarized astrocyte membrane potential (V(m) ), and the THIP-induced currents reversed at the voltages between -75.3 and -78.3 mV, corresponding to a [Cl(-) ](i) of 3.1-3.9 mM that favored a passive distribution of Cl(-) anions across astrocyte membrane. Further analysis showed that GABA(A) -R-induced V(m) depolarization was ascribed to HCO(3) (-) efflux, while a passively distributed Cl(-) mediated no net flux or influx of Cl(-) that leads to an unchanged or hyperpolarized V(m) . In addition to a rapidly activated GABA(A) -R current component, GABA and THIP also induced a delayed inward current (DIC) in 63% of astrocytes. The DIC became manifest after agonist withdrawal and enhanced in amplitude with increasing agonist application duration or concentrations. Astrocytic two-pore domain K(+) channels (K2Ps), especially TWIK-1, appeared to underlie the DIC, because (1) acidic intracellular pH, as a result of HCO(3) (-) efflux, inhibited TWIK-1, (2) the DIC remained in the Cs(+) recording solutions that inhibited conventional K(+) channels, and (3) the DIC was completely inhibited by 1 mM quinine but not by blockers for other cation/anion channels. Altogether, HCO(3) (-) efflux through activated GABA(A) -R depolarizes astrocyte V(m) and induces a delayed inhibition of K2Ps K(+) channels via intracellular acidification.
authors.affiliation: Department of Neuroscience, The Ohio State University Wexner Medical Center, Columbus, Ohio, USA.
authors.forename: Bao-Feng
authors.initials: BF
authors.lastname: Ma
authors.forename: Min-Jie
authors.initials: MJ
authors.lastname: Xie
authors.forename: Min
authors.initials: M
authors.lastname: Zhou
mesh_terms: D000818:Animals; D001253:Astrocytes / Q000502:physiology*; D001639:Bicarbonates / Q000378:metabolism*; D006624:Hippocampus / Q000502:physiology*; D008564:Membrane Potentials / Q000502:physiology*; D018408:Patch-Clamp Techniques; D015221:Potassium Channels / Q000502:physiology*; D051381:Rats; D017207:Rats, Sprague-Dawley; D011963:Receptors, GABA-A / Q000378:metabolism*
chemical_list: D001639:Bicarbonates; D015221:Potassium Channels; D011963:Receptors, GABA-A