Bicarbonate efflux via GABA A receptors depolarizes membrane potential and inhibits two‐pore domain potassium channels of astrocytes in rat hippocampal slices

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. © 2012 Wiley Periodicals, Inc.