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 (GABAA-R) in astrocytes. However, it remains controversial in regard to the intracellular Cl− concentration ([Cl−]i) and the functional role of anion-selective GABAA-R in astrocytes. In gramicidin perforated-patch recordings from rat hippocampal CA1 astrocytes, GABA and GABAA-R specific agonist THIP depolarized astrocyte membrane potential (Vm), and the THIP induced currents reversed at the voltages between −75.3 to −78.3 mV, corresponding to a [Cl−]i of 3.1 – 3.9 mM that favors a passive distribution of Cl− anions across astrocyte membrane. Further analysis showed that GABAA-R induced Vm depolarization is ascribed to HCO3− efflux, while a passively distributed Cl− mediates no net flux or influx of Cl-that leads to an unchanged or hyperpolarized Vm. In addition to a rapidly activated GABAA-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 HCO3− 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, HCO3− efflux through activated GABAA-R depolarizes astrocyte Vm and induces a delayed inhibition of K2Ps K+ channels via intracellular acidification.

Fast Ca2+ responses in astrocyte end‐feet and neurovascular coupling in mice

“…High dose THIP (100 µM) reduced CBF and fEPSP responses (Jessen et al, ) in accordance with a reduced fast Ca 2+ response in astrocyte end‐feet. A similar dose of THIP depolarizes astrocytes in hippocampal slices, blocking the two‐pore domain K + channels (Ma, Xie, & Zhou, ) and the release of vasodilator K + .…”

Molecular assessment of the effect of light and heterotrophy in the scleractinian coral Stylophora pistillata

“…Conversely, Vidal-Dupiol et al [49] observed the upregulation of several CAs under acidification stresses at pH 7.8 and 7.4, but downregulation at a lower pH (7.2). Finally, in HLU corals, several genes related to the solute carrier proteins (SLC) were affected by high light stress and downregulated: SLC6A1 is an amino acid transporter, [50]; SLC26-A6, which functions as a bicarbonate/chloride exchanger in vertebrates [51], was also downregulated in corals experiencing heat stress [43]; SLC7A4 or CTR4 is a cationic amino acid transporter. Its downregulation can impact protein or membrane formation.…”

The contribution of TWIK-1 channels to astrocyte K+ current is limited by retention in intracellular compartments

“…We used 14 mM Na + and 3 mM Cl − as they are physiological in astrocyte (Kelly et al, 2009; Ma et al, 2012a). The Cs + -based electrode solution was made by equimolar substitution of K-gluconate with Cs-gluconate.…”