Glutamate is a neurotransmitter released by approximately 40% of all synaptic terminals in the CNS. It and other related amino acid neurotransmitters are deemed excitatory amino acids because they have the ability to induce depolarization of the neuronal membrane and stimulate an action potential at the post-synaptic terminal. This is accomplished via three membrane bound receptors that regulate ion flow. This experiment will focus on the NMDA (N-methyl-D-aspartate) receptor, which has a membrane spanning ion channel that is permeable to sodium, potassium, and calcium ions. All of the ions that pass through the NMDA receptor have specific roles in the depolarization process of the neuronal membrane. Yet if any of these ions, especially calcium ions begin to accumulate in the intracellular space of nerve cell, they can be toxic. This increase in intracellular calcium concentration has been linked to the toxicity of glutamate.
This hypothesized mechanism of glutamate toxicity may be at the heart of such neurodegenerative diseases as: Parkinson’s disease, Huntington’s disease, Alzheimer’s, amyotrophic lateral sclerosis (ALS), hypoxia, and ischemia.
An added aspect to this mechanism that may increase, induce, or potenciate glutamate toxicity and neuronal degeneration is oxidative stress. With age or periods of anoxia, neuronal cells produce less ATP (adenosine triphosphate) which is necessary for complete functioning of the cell. When glutamate allows ions such as sodium, potassium, and calcium to enter a neuronal cell, it is the duty of the sodium-potassium ATPase and calcium ATPase to relieve the cell of these potentially toxic ions. With short or extended periods of oxidative stress, the ATPases can not return the cell’s ionic concentrations to functioning and stable equilibrium and cell death ensues.
Nelson Alexander, ’97
Sponsor: Barbara Christie-Pope