Page - (000276) - in Biomedical Chemistry: Current Trends and Developments

name implies, allow ions to enter or leave the cell via an intrinsic ion channel. iGluRs are typically heteromultimeric, integral membrane proteins that are composed of four subunits that form a transmembrane ion channel. This channel is allosterically connected to the agonist- binding site and upon binding to glutamate or an exogenous agonist, the channel portion opens and allows cations to pass into the cell which directly depolarize the membrane potential. 3.2.2 Glutamate and Glutamate Receptors The postsynaptic iGluR composition has been found to mediate the ionic makeup of the current that results from glutamate binding. The iGluRs are subdivided into NMDA receptors and non-NMDA receptors with the latter being further divided into AMPA receptors and kainate receptors. The AMPA receptors, named after the synthetic agonist α-amino-3- hydroxy-5-methyl-4-isoxazolepropionic acid, are located on the acceptor, or postsynaptic, dendrite where they bind neurotransmitters, causing a conformational change in the receptor protein structure that opens intrinsic sodium ion channels. AMPA receptors are responsible for the vast majority of excitatory neurotransmission and they open quickly in response to glutamate and close fast as well. The influx of sodium ions alters the electrical potential of the postsynaptic cell, producing a local signal that, after summation and integration at the neuron and then circuit level, ultimately results in cognition or action. Another family of iGluRs is the kainate receptors. These appear to be more related to AMPA receptors, but they are still the subject of ongoing research and their roles in either normal signaling or excitotoxicity has not been fully explored. If the cellular polarization is above a certain threshold, neighboring NMDA receptors, named after the synthetic agonist N-methyl-D-aspartate, fully or partially eject an ion channel- bound magnesium ion allowing calcium to flow into the cell. The entry of calcium then sets off myriad intracellular events, not least of which is activation of calcium-activated kinases and, eventually, synaptic potentiation (Lisman, 2012). A change in the communication strength between adjacent neurons arises from trafficking of receptors to or from the synaptic zone and it is presently thought that this molecular