Glutamate Ionotropic Receptors: AMPA and NMDA receptors

There are two main types of Glutamate Ionotropic Receptors involved in synaptic transmission: the AMPA and NMDA receptors.

The AMPA receptor is responsible for the normal EPSP (excitatory postsynaptic potential) generated by glutamatergic neurones

The NMDA receptor can produce very strong depolarisations, but only when the membrane is already depolarised; this changeover
occurs when magnesium ions are displaced from their binding site, allowing calcium ions to move through the channel into the neurone.

A third glutamatergic ionotropic receptor, the Kainate receptor, appears to be more involved in neuroplasticity than neurotransmission

Ionotropic receptors are ion channels in the cell membrane which can be opened by the attachment of a ligand to a binding site.
Glutamate is a ligand that opens two ion channels, one weak, one strong, and known as the AMPA and NMDA channels.

The EPSP is due to glutamate acting on the AMPA receptor

In dendritic spines, the number of AMPA receptors in the post-synaptic membrane can change significantly because of AMPA receptor
trafficking. AMPA receptors in the membrane can be internalised and sequestered within an internal reservoir; AMPA receptor can also
be re-inserted into the post-synaptic membrane. So there is an ongoing process of endocytosis, recycling, and re-insertion into the post-
synaptic membrane: internalisation is achieved during long-term depression, and re-insertion occurs during long-term potentiation.

NMDA ionotropic channels do not open in response to glutamate until the cell membrane is sufficiently depolarised as a result of AMPA
receptor activation. Once depolarised to this level, a magnesium ion that occupies the pore is displaced, allowing a strong calcium current
to enter the neurone. Calcium acts as a second messenger and activates a number of enzymes and intracellular cascades.
N-methyl-D-aspartate receptor (also known as the NMDA
receptor or NMDAR)

There are eight variants of the NR1 subunit produced by

alternative splicing of GRIN1:[10]
• NR1-1a, NR1-1b; NR1-1a is the most abundantly
expressed form.
• NR1-2a, NR1-2b;
• NR1-3a, NR1-3b;
• NR1-4a, NR1-4b;
The α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic
acid receptor (AMPA receptor, AMPAR)