Glutamate Receptors

Ionotropic Glutamate Receptors

There are 3 main types of ionotropic receptor for glutamate: NMDA, AMPA and kainate, so named after their original agonists.

NMDA receptors are assembled from seven types of subunit (GluN1, GluN2A, GluN2B, GluN2C, GluN2D, GluN3A, GluN3B).  The subunits that make up AMPA receptors (GluA1-4) and kainate receptors (GluK1-5), are closely related to, but distinct from, GluN subunits.  The subunit arrangement of a receptor can have important effects on its function as well as its structure, e.g. AMPA can possess two versions of GluA2- one which makes the AMPA receptor permeable to calcium, the other which makes it impermeable.

AMPA receptors facilitate fast excitatory transmission (fast EPSP- excitatory post-synaptic potential), while NMDA receptors facilitate slow transmission (slow EPSP).  NB Conventionally, fast EPSPs are usually produced via the opening of ion channels and take just several ms to work, whereas slow EPSP’s are usually G-protein coupled receptor mediated and take longer and may require more stimulation.  In the NMDAR (a ligand-gated ion channel)- this is not the case.  In fact, the NMDAR seems to show slow kinetics.  Also, under resting conditions, an Mg(2+) ion acts to block the NMDA receptor from opening.  It is released once the cell membrane is persistently depolarised.  As a result, NMDARs do not contribute to basal levels of excitation.  On top of all of this, NMDA receptors require the binding of glycine as well as glutamate/NMDA to open.  The complexity of the NMDA receptor may be protective against glutamate mediated neurotoxicity.

Ionotropic receptors are found in the cortex, basal ganglia and sensory pathways.  NMDA and AMPA receptors are generally found together throughout these areas whereas kainate receptors are a little more selective.

Metabotropic Glutamate Receptors

There are 8 different types of these G-protein coupled glutamate receptors (mGlu(1-8)).  They are arranged as homodimers connected by a disulfide bridge.

They are widely distributed throughout the CNS in neurons and glial cells.  They regulate excitability and transmission via molecular signalling.  Group 1 receptors generally are found postsynaptically and generally increase excitability by raising intracellular calcium levels.  Group 2 and 3 receptors are pre-synaptic and generally reduce cellular excitability.

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