Matrix Metalloproteinase-9 Reversibly Affects the Time Course of NMDA-Induced Currents in Cultured Rat Hippocampal Neurons

Matrix Metalloproteinase 9 (MMP-9) has been demonstrated to play a crucial role in maintenance of NMDA receptor-dependent LTP and in lateral mobility of these receptors. However, the effect of MMP-9 on NMDA receptor (NMDAR) functional properties is unknown. For this purpose we have investigated the impact of recombinant MMP-9 on the whole-cell NMDAR-mediated current responses in cultured hippocampal neurons. Treatment with MMP-9 induced a reversible acceleration of desensitization and deactivation kinetics but had no effect on current amplitude. Interestingly, phorbol ester, a PKC activator known to enhance NMDAR lateral mobility, induced kinetic changes of currents similar to those produced by MMP-9. In conclusion, our results show that MMP-9 reversibly modulates the NMDAR kinetics and raise a possibility that this modulation could be related to the lateral mobility of these receptors. (C) 2009 Wiley-Liss, Inc.