Dr. Nowak's research is aimed at obtaining additional knowledge of the mechanisms underlying N-methyl-D-aspartate (NMDA) receptor-channel function in mammalian brain neurons. The NMDA subclass of glutamate receptors are coupled to nonselective cation channels permeable to Ca2+ and blocked by Mg2+ in a voltage-dependent way. It is Ca2+ entry through NMDA channels which is thought to serve as a trigger for some of the plastic changes observed during nervous system development and in learning. Thus, the overall goal of the research is to address the question, "how can the apparently high influx of Ca2+ through NMDA channels as demonstrated by dye measurements be reconciled with all of the factors which would tend to limit Ca2+ entry"? One possible explanation is that there is more diversity among NMDA receptor-channels than previously recognized with some putative forms of the channels being relatively insensitive to blockage by Mg2+. Dr. Nowak's first series of experiments will involve an examination of the similarities and differences in biophysical parameters between NMDA channels in cerebellar granule cells and cortical neurons where different forms of the channels are predicted to occur. She will then perform additional experiments designed to examine the potential sites of Ca2+ interaction with NMDA channels. All of the proposed experiments are designed to explore the fundamental role(s) played by two divalent cations found in physiological fluids, namely Ca2+ and Mg2+ ions, in regulating the functioning of a major class of neurotransmitter-activated receptor-channels in brain neurons.
