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The Journal of Neuroscience, January 7, 2004, 24(1):103-111; doi:10.1523/JNEUROSCI.4473-03.2004
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Cellular/Molecular
Climbing Fiber Activation of EAAT4 Transporters and Kainate Receptors in Cerebellar Purkinje Cells
Yanhua H. Huang,1
Margaret Dykes-Hoberg,2
Kohichi Tanaka,3
Jeffrey D. Rothstein,2 and
Dwight E. Bergles1
Departments of 1Neuroscience and 2Neurology, Johns Hopkins University, Baltimore, Maryland 21205, and 3Laboratory of Molecular Neuroscience, School of Biomedical Science and Medical Research Institute, Tokyo Medical and Dental University, Tokyo, Japan 113-8510
Cerebellar Purkinje cells (PCs) express two glutamate transporters, EAAC1 (EAAT3) and EAAT4; however, their relative contribution to the uptake of glutamate at synapses is not known. We found that glutamate transporter currents recorded at climbing fiber (CF)-PC synapses are absent in mice lacking EAAT4 but unchanged in mice lacking EAAC1, indicating that EAAT4 is preferentially involved in clearing glutamate from CF synapses. However, comparison of CF synaptic currents between wild-type and transporter knock-out mice revealed that ionotropic glutamate receptors are responsible for >40% of the current previously attributed to transporters, indicating that PCs remove <10% of the glutamate released by the CF. The receptors responsible for the nontransporter component accounted for 5% of the CF EPSC, had a slower time course and lower occupancy than AMPA receptors at CF synapses, and exhibited pharmacological properties consistent with kainate receptors. In GluR5 knock-out mice, this current was dramatically reduced, indicating that CF excitation of PCs involves two distinct classes of ionotropic glutamate receptors, AMPA receptors and GluR5-containing kainate receptors.
Key words: cerebellum; EAAT4; EAAC1; Purkinje neuron; GluR5; kainate receptor; EPSC; glutamate transporter
Received Oct 1, 2003;
revised November 3, 2003;
accepted November 3, 2003.
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