Functional regulation of N-methyl-D-aspartate receptors by serine/threonine protein kinases

grantor: University of TorontoThe N-methyl-D-aspartate (NMDA) subtype of glutamate receptor plays a crucial role in a variety of neuronal processes such as long-term potentiation (LTP). A major consequence of NMDA receptor activation is a large influx of calcium into the cell which in turn leads to the activation of protein kinases. Chen and Huang (1992) reported that PKC enhances NMDA currents by reducing the Mg$\sp{2+}$ sensitivity of these channels in trigeminal neurons. In the hippocampal neurons activation of PKC has been reported to enhance or reduce the NMDA activated currents (Wang et al., 1994, Markram and Segal 1992). In these experiments, we examined the effects of intracellular perfusion of PKCM (a constituitively active form of PKC) on NMDA-evoked currents in cultured and acutely isolated hippocampal neurons. Also the effects of Ca$\sp{2+}$/calmodulin dependent protein kinase II (CaMK II) on NMDA-evoked currents were examined. Results indicate that PKC acts via a phosphorylation-dependent mechanism to enhance NMDA-evoked currents in hippocampal neurons without altering the Mg$\sp{2+}$ sensitivity of the channels. (Abstract shortened by UMI.)M.Sc