Glycine Potentiates AMPA Receptor Function through Metabotropic Activation of GluN2A-Containing NMDA Receptors.
NMDA receptors are Ca2+-permeable ion channels. The activation of NMDA receptors requires agonist glutamate and co-agonist glycine. Recent evidence indicates that NMDA receptor also has metabotropic function. Here we report that in cultured mouse hippocampal neurons, glycine increases AMPA receptor-mediated currents independent of the channel activity of NMDA receptors and the activation of glycine receptors. The potentiation of AMPA receptor function by glycine is antagonized by the inhibition of ERK1/2. In the hippocampal neurons and in the HEK293 cells transfected with different combinations of NMDA receptors, glycine preferentially acts on GluN2A-containing NMDA receptors (GluN2ARs), but not GluN2B-containing NMDA receptors (GluN2BRs), to enhance ERK1/2 phosphorylation independent of the channel activity of GluN2ARs. Without requiring the channel activity of GluN2ARs, glycine increases AMPA receptor-mediated currents through GluN2ARs. Thus, these results reveal a metabotropic function of GluN2ARs in mediating glycine-induced potentiation of AMPA receptor function via ERK1/2 activation.
Department of Physiology, Toronto Western Research Institute, School of Medicine, University of Toronto Toronto, Canada.
Li-Jun
LJ
Li
Department of Physiology and Cell Biology, University of Nevada School of MedicineReno, NV, USA; Department of Neurosurgery, Southwest HospitalChongqing, China.
Rong
R
Hu
Department of Physiology and Cell Biology, University of Nevada School of Medicine Reno, NV, USA.
Brendan
B
Lujan
Department of Neurology, Central Hospital of Wuhan Wuhan, China.
Juan
J
Chen
Department of Neurosurgery, Zhongnan Hospital, Wuhan University School of Medicine Wuhan, China.
Jian-Jian
JJ
Zhang
Department of Physiology and Cell Biology, University of Nevada School of Medicine Reno, NV, USA.
Yasuko
Y
Nakano
Department of Physiology and Cell Biology, University of Nevada School of Medicine Reno, NV, USA.
Tian-Yuan
TY
Cui
Department of Physiology and Cell Biology, University of Nevada School of Medicine Reno, NV, USA.
Ming-Xia
MX
Liao
Department of Neurosurgery, Zhongnan Hospital, Wuhan University School of Medicine Wuhan, China.
Jin-Cao
JC
Chen
Department of Biology, Boston University Boston, MA, USA.
Heng-Ye
HY
Man
Department of Neurosurgery, Southwest Hospital Chongqing, China.
Hua
H
Feng
Department of Physiology, Toronto Western Research Institute, School of Medicine, University of TorontoToronto, Canada; Department of Physiology and Cell Biology, University of Nevada School of MedicineReno, NV, USA; Department of Neurosurgery, Zhongnan Hospital, Wuhan University School of MedicineWuhan, China; Department of Physiology, School of Basic Medical Sciences, Wuhan University School of MedicineWuhan, China.
Qi
Q
Wan
AMPA receptor; ERK1/2; HEK293 cells; NMDA receptor; glycine; hippocampal neurons