Climbing fiber activation of EAAT4 transporters and kainate receptors in cerebellar Purkinje cells.
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.
Huang
Yanhua H
YH
Department of Neuroscience, Johns Hopkins University, Baltimore, Maryland 21205, USA.
Dykes-Hoberg
Margaret
M
Tanaka
Kohichi
K
Rothstein
Jeffrey D
JD
Bergles
Dwight E
DE
D027322:Amino Acid Transport System X-AG / Q000235:genetics / Q000378:metabolism* / Q000502:physiology; D000818:Animals; D002478:Cells, Cultured; D002531:Cerebellum / Q000166:cytology*; D004553:Electric Conductivity; D050580:Excitatory Amino Acid Transporter 3; D050581:Excitatory Amino Acid Transporter 4; D050491:Glutamate Plasma Membrane Transport Proteins; D007700:Kinetics; D051379:Mice; D018345:Mice, Knockout; D009412:Nerve Fibers / Q000737:chemistry / Q000502:physiology; D011689:Purkinje Cells / Q000502:physiology*; D051381:Rats; D017470:Receptors, Glutamate / Q000145:classification / Q000502:physiology; D018092:Kainic Acid Receptors / Q000378:metabolism* / Q000502:physiology; D027981:Symporters / Q000502:physiology; D013569:Synapses / Q000737:chemistry / Q000502:physiology
D027322:Amino Acid Transport System X-AG; D050580:Excitatory Amino Acid Transporter 3; D050581:Excitatory Amino Acid Transporter 4; D050491:Glutamate Plasma Membrane Transport Proteins; D017470:Receptors, Glutamate; D018092:Kainic Acid Receptors; D027981:Symporters; C493399:Slc1a1 protein, mouse; C493398:Slc1a1 protein, rat; C493390:Slc1a6 protein, mouse; C493389:Slc1a6 protein, rat