期刊
GLIA
卷 65, 期 2, 页码 388-400出版社
WILEY-BLACKWELL
DOI: 10.1002/glia.23098
关键词
Bergmann glia; fluorescence lifetime imaging; glial chloride switch; EAAT
资金
- Deutsche Forschungsgemeinschaft [SPP 1757, Ro2327/8-1]
Astrocytic volume regulation and neurotransmitter uptake are critically dependent on the intracellular anion concentration, but little is known about the mechanisms controlling internal anion homeostasis in these cells. Here we used fluorescence lifetime imaging microscopy (FLIM) with the chloride-sensitive dye MQAE to measure intracellular chloride concentrations in murine Bergmann glial cells in acute cerebellar slices. We found Bergmann glial [Cl-](int) to be controlled by two opposing transport processes: chloride is actively accumulated by the Na+-K+-2Cl(-) cotransporter NKCC1, and chloride efflux through anion channels associated with excitatory amino acid transporters (EAATs) reduces [Cl-](int) to values that vary upon changes in expression levels or activity of these channels. EAATs transiently form anion-selective channels during glutamate transport, and thus represent a class of ligand-gated anion channels. Age-dependent upregulation of EAATs results in a developmental chloride switch from high internal chloride concentrations (51.6 +/- 2.2 mM, mean +/- 95% confidence interval) during early development to adult levels (35.3 +/- 0.3 mM). Simultaneous blockade of EAAT1/GLAST and EAAT2/GLT-1 increased [Cl-](int) in adult glia to neonatal values. Moreover, EAAT activation by synaptic stimulations rapidly decreased [Cl-](int). Other tested chloride channels or chloride transporters do not contribute to [Cl-](int) under our experimental conditions. Neither genetic removal of ClC-2 nor pharmacological block of K+-Cl- cotransporter change resting Bergmann glial [Cl-](int) in acute cerebellar slices. We conclude that EAAT anion channels play an important and unexpected role in adjusting glial intracellular anion concentration during maturation and in response to cerebellar activity.
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