Astrocytic Ca2+-activated anion channel, Bestrophin-1, is permeable to glutamate and GABA
- Astrocytic Ca2+-activated anion channel, Bestrophin-1, is permeable to glutamate and GABA
- 오수진; 윤보은; 이창준
- astrocyte; bestrophin; glutamate; gaba
- Issue Date
- Bestrophin, which is known to be the gene linked to Best's vitelliform macular dystrophy, has been suggested to encode a functional Ca2+- activated anion channel (CAAC) in various nonneuronal tissues and peripheral neurons. Recently, we have demonstrated that mouse astrocytes express functional Ca2+-activated anion channel that is permeable to large anions such as isethionate and glutamate. This channel is encoded mostly by mouse Bestrophin-1 (mBest1). Astrocytes are known to release gliotransmitters such as glutamate in Ca2+- dependent fashion. Here we hypothesized that release of major excitatory and inhibitory transmitters, glutamate and g-aminobutyric acid (GABA) could be mediated by mBest1 channel. We confirmed the functional role of Best1 as a CAAC in cultured astrocytes. The mBest1-mediated CAAC was significantly reduced by gene silencing using mBest1-shRNA and rescued by shRNA insensitive form of mBest1. Then, we determined the permeability of mBest1 to glutamate and GABA with whole-cell patch-clamp analysis using HEK293T cells heterologously expressing the full-length mBest1. The glutamate and GABA permeability of mBest1 channel was examined by replacing Cl– in the intracellular pipette solution with glutamate and GABA. The reversal potential of the glutamate and GABA current shifted toward a more negative potential compared to Cl–, indicating a lower permeability to glutamate and GABA than to Cl–. However, estimated relative permeability ratio of glutamate (Pglutamate / PCl = 0.49) and GABA (PGABA / PCl = 0.19) to Cl–, demonstrating that glutamate and GABA can permeate significantly through mBest1 channel. These results implicate that mBest1 could mediate astrocytic glutamate and GABA release, proposing an important role for neuron-glia interaction in regulating brain function.
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