Abstract
Phosphatase IIb (calcineurin, CaN) can reduce N-methyl-D-aspartate (NMDA) synaptic responses by enhancing glycine-independent desensitization. We examined the action of CaN on desensitization in recombinant NMDA receptors comprised of NMDA receptor 1 (NR1) and NR2A subunits. The C-terminus of NR2A, but not NR1, was critical for modulation of desensitization by CaN. Alanine-scanning mutagenesis indicated that serines 900 and 929 in NR2A altered desensitization, as did inhibition of tyrosine phosphatases. Our data suggest that dephosphorylation-dependent regulation of the C-terminus of NR2A increases desensitization of NMDA receptors, providing an additional mechanism for modulation of synaptic signals.
Original language | English (US) |
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Pages (from-to) | 593-602 |
Number of pages | 10 |
Journal | Neuropharmacology |
Volume | 42 |
Issue number | 5 |
DOIs | |
State | Published - 2002 |
Keywords
- Calcineurin
- Desensitization
- Mutagenesis
- NMDA receptors
- Patch-clamp
- Tyrosine phosphatases
ASJC Scopus subject areas
- Pharmacology
- Cellular and Molecular Neuroscience