NMDAR ion channels are found in neurons and are frequent targets of research efforts. In addition to potentially playing a key role in learning and memory, it is also a target for research for therapeutic solutions against Alzheimer’s disease, Parkinson’s disease, schizophrenia, and depression. Dr. Kevin S. Jones and doctoral student, Nichelle Jackson, from the University of Michigan, are exploring the effects of two NMDAR receptor blockers, memantine and MK-801. Despite both drugs binding to the same region of the ion channel, these two antagonists have exceptionally different effects. Whilst memantine is used to treat the symptoms of Alzheimer’s disease, MK-801 is known to induce psychotic effects. Nichelle hypothesizes that these different effects arise from differences in how the drugs interact with the ion channel.

The goal of Nichelle’s research is to identify structural elements within the channel pore that mediate these differences. She uses site-directed mutagenesis to introduce point mutations into the NDMA channels to determine structural elements within the channel pore that are responsible for the differing effects of memantine and MK-801.

The group uses human embryonic kidney cells as a heterologous expression system to measure how the mutations impact changes in the amplitude and waveform of NMDAR current after the drugs block the channel pore. In addition to requiring extremely sensitive equipment to detect small changes in electrical current, the group also needed a way to deliver the antagonists with high temporal precision.