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- W2895524139 abstract "Excitatory amino acid transporters called EAATs are dual function proteins, they are secondary active glutamate transporters as well as anion channels. While the altered anion channel function of glial EAATs is associated with severe human diseases, nothing is known about their physiological role in proper brain function. Glial cells are known to actively accumulate chloride. These cells exhibit a stable negative resting potential, so that anion channels may lower [Cl-]int via passive chloride effluxes. Here the role of the glial EAAT isoforms, EAAT1/GLAST and EAAT2/GLT1, for regulating intracellular chloride concentrations in Bergmann glia in the cerebellar cortex was studied using fluorescent lifetime imaging microscopy (FLIM) with the chloride-sensitive fluorescent dye MQAE in acute cerebellar slices. In WT mice and EAAT1/GLAST knock-out (Slc1a3-/-), intracellular chloride concentrations differ significantly (WT = 34.2 mM, Slc1a3-/- 40.9 mM). A comparable increase in [Cl-]int was measured in WT glial cells after isoform-specific blocking of EAAT1/GLAST using UCPH-101. Since, glial EAATs are developmentally upregulated, the age dependence of [Cl-]int in Bergmann glia of wild type and Slc1a3-/- was investigated, and the glial chloride switch was newly-discovered. Starting with high [Cl-]int of around 50 mM in young animals, the [Cl-]int decreased to the adult level, corresponding to the upregulation of cerebellar EAAT1/GLAST and EAAT2/GLT1 expression. Upon substrate application as well as electrical stimulation dynamic changes in the [Cl-]int in Bergmann glia due to glial EAATs could be observed. Changes in the glial [Cl-]int may affect secondary active transport over the glial plasma membrane, such as in case of GABA uptake mediated by GAT. Hence, changes in [Cl-]int can stimulate the GABA uptake and affect synaptic transmission. Bergmann glia and cerebellar neurons are tightly functional coupled, thus glial EAATs may modulate cell migration during cerebellar maturation and influence synaptic transmission. This work characterized for the first time the cellular function of anion channels associated with EAAT1 and EAAT2. Furthermore, the developmental glial chloride switch in cerebellar Bergmann glia was discovered and characterized." @default.
- W2895524139 created "2018-10-12" @default.
- W2895524139 creator A5024515241 @default.
- W2895524139 date "2016-01-01" @default.
- W2895524139 modified "2023-09-27" @default.
- W2895524139 title "CELLULAR ROLES OF GLUTAMATE TRANSPORTER-ASSOCIATED ANION CHANNELS IN GLIAL CELLS" @default.
- W2895524139 hasPublicationYear "2016" @default.
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