TY - JOUR
T1 - Synaptic desensitization of NMDA receptors by calcineurin
AU - Tong, Gang
AU - Shepherd, Dawn
AU - Jahr, Craig E.
PY - 1995/3/10
Y1 - 1995/3/10
N2 - Desensitization is a phenomenon that is common to many ligand-gated ion channels but has been demonstrated only rarely with physiological stimulation. Numerous studies describe desensitization of the N-methyl-D-aspartate (NMDA) subtype of glutamate receptor by exogenous agonists, but whether synaptic stimulation causes desensitization has been unknown. Synaptic stimulation of NMDA receptors on rat hippocampal neurons resulted in desensitization that was prevented by intracellular 1,2-bis(o-aminophenoxy)ethane-N,N,N'N'-tetraacetic acid (BAPTA), adenosine-5'-O-(3-thiotriphosphate) (ATP-γ-S), or inhibitors of phosphatase 28 (calcineurin), but not by inhibitors of phosphatases 1 and 2A or of tyrosine phosphatases. Synaptic NMDA receptors may fluctuate between phosphorylated and dephosphorylated forms, depending on the rate of synaptic stimulation and the magnitude of the associated influx of calcium through NMDA receptors.
AB - Desensitization is a phenomenon that is common to many ligand-gated ion channels but has been demonstrated only rarely with physiological stimulation. Numerous studies describe desensitization of the N-methyl-D-aspartate (NMDA) subtype of glutamate receptor by exogenous agonists, but whether synaptic stimulation causes desensitization has been unknown. Synaptic stimulation of NMDA receptors on rat hippocampal neurons resulted in desensitization that was prevented by intracellular 1,2-bis(o-aminophenoxy)ethane-N,N,N'N'-tetraacetic acid (BAPTA), adenosine-5'-O-(3-thiotriphosphate) (ATP-γ-S), or inhibitors of phosphatase 28 (calcineurin), but not by inhibitors of phosphatases 1 and 2A or of tyrosine phosphatases. Synaptic NMDA receptors may fluctuate between phosphorylated and dephosphorylated forms, depending on the rate of synaptic stimulation and the magnitude of the associated influx of calcium through NMDA receptors.
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U2 - 10.1126/science.7878472
DO - 10.1126/science.7878472
M3 - Article
C2 - 7878472
AN - SCOPUS:0028929331
SN - 0036-8075
VL - 267
SP - 1510
EP - 1512
JO - Science
JF - Science
IS - 5203
ER -