CA2-INDEPENDENT REDUCTION OF N-METHYL-D-ASPARTATE CHANNEL ACTIVITY BYPROTEIN-TYROSINE-PHOSPHATASE()

Regulation of ion channel function by intracellular processes is funda mental for controlling synaptic signaling and integration in the nervo us system. Currents mediated by N-methyl-D-aspartate (NMDA) receptors decline during whole-cell recordings and this may be prevented by ATP. We show here that phosphorylation is necessary to maintain NMDA curre nts and that the decline is not dependent upon Ca2+. A protein tyrosin e phosphatase or a peptide inhibitor of protein tyrosine kinase applie d intracellularly caused a decrease in NMDA currents even when ATP was included. On the other hand, pretreating the neurons with a membrane- permeant tyrosine kinase inhibitor occluded the decline in NMDA curren ts when ATP was omitted. In inside-out patches, applying a protein tyr osine phosphatase to the cytoplasmic face of the patch caused a decrea se in probability of opening of NMDA channels. Conversely, open probab ility was increased by a protein tyrosine phosphatase inhibitor. These results indicate that NMDA channel activity is reduced by a protein t yrosine phosphatase associated with the channel complex.