Page - (000278) - in Biomedical Chemistry: Current Trends and Developments

neurons of ALS patients, more extensively in those expressing Q/R site- unedited GluA2 mRNA than those expressing only Q/R site-edited GluA2 mRNA. These findings suggest that antagonism of calcium-permeable AMPA receptors could slow disease progression, a topic we will discuss later in this manuscript. 3.2.2.2 Kainate Receptors Kainate receptors are also heterotetrameric ion channels assembled from subunits GluA5-7 and KA1-2 (also known as GluK1-2). The properties of kainate channels are similar to AMPARs in that they allow ion flux if glutamate activates the channel. Further, kainate receptors are mostly impermeable to calcium. One main difference between AMPA and kainate receptors is their subcellular location. While most AMPA receptors are located at the postsynaptic membrane, kainate receptors have been found on the presynaptic side as well as the postsynaptic side. It remains unclear if presynaptic kainate receptor stimulation by glutamate results in more or less vesicular release of glutamate into the synapse, though in the case of neuronal necrosis and ischemia, it very likely does. These are discussed later in this chapter. The function of postsynaptic kainate receptors is similar to that of AMPA receptors in that depolarization via glutamate-evoked kainate channel current can unplug the magnesium ion blocking NMDA receptors, thus leading to calcium entry into the postsynaptic spine. 3.2.2.3 NMDA Receptors NMDA receptors are heterotetramers and are assembled from three major families of subunits. The NR1 subunit is ubiquitously expressed, there are four NR2 subunits (A-D), and two NR3 members (A and B). Most NMDA receptors that have been studied to date contain both NR1 and NR2 subunits and they share the common attributes of being activated by glutamate but normally being blocked by a magnesium ion that is removed upon strong stimulation of the postsynaptic spine. Besides glutamate, it was found that glycine was a required co-agonist to elicit NMDA channel opening.