Regulation of NMDA receptors in cultured hippocampal neurons by protein phosphatases 1 and 2A

Abstract
PHOSPHORYLATION of glutamate receptors is probably an important mechanism for modulating excitatory transmission1–4. However, there is little direct evidence to indicate which protein phosphatases can dephosphorylate glutamate5 or other ligand-gated channels6, although it is known that protein phosphatases 1 and 2A play a major part in modulating voltage7–10 and second-messenger-gated channels11. Here we report that in cultured hippocampal neurons, the N-methyl-D-aspartate (NMDA) receptor can be regulated by endogenous and exogenous serine/threonine protein phosphatases. Phosphatase inhibitors enhanced NMDA currents recorded using the perforated patch technique13 or in cell-attached patches, whereas protein phosphatases 1 or 2A decreased the open probability of these channels in inside-out patches.