抄録
GLAST and GLT-1 are glial glutamate transporters that regulate the concentration of glutamate in the synaptic cleft. In the Bergmann glial processes ensheathing excitatory synapses on Purkinje cells in the cerebellum, GLAST is expressed 6 times more abundantly than GLT-1. Unexpectedly, no change was detected in the kinetics of EPSCs evoked by climbing fiber (CF) stimulation in cerebellar slices in GLAST-deficient mice as compared with those in the wild-type mice (WT). This suggested that GLT-1 contributed to the uptake of glutamate in CF-Purkinje cell synapses. Here we aimed to clarify the role of GLT-1 in both WT and GLAST-deficient mice using dihydrokainate (DHK), a selective GLT-1 blocker. DHK caused no change in the kinetics of CF-EPSCs in WT. In the presence of cyclothiazide (CTZ), that not only reduces the desensitization of AMPA receptors but also increases the affinity of glutamate to the receptors, however, DHK significantly prolonged the decay time constant of CF-EPSCs in WT. Although there was no change in the decay time constant of CF-EPSCs between WT and GLAST-deficient mice in the normal saline, it was significantly longer in the mutant mice in the presence of CTZ. Taken together, these results indicate that GLT-1 plays a partial role in the uptake of glutamate in WT, and that it compensates a large portion of the function of GLAST in GLAST-deficient mice although the compensation is incomplete. The GLAST-deficient mice were kindly provided by Prof. Kohichi Tanaka. [Jpn J Physiol 55 Suppl:S149 (2005)]
