AMPA receptors mediate fast synaptic transmission. The name is derived from the ability of a synthetic glutamate analog, AMPA to activate the receptor. The membrane becomes more permeable to sodium and potassium, which move across the membrane according to their electrochemical equilibrium potentials, i.e. small numbers of sodium ions move into the cell and potassium moves out. |
AMPA receptors (AMPARs) induce small depolarisations in the post-synaptic membrane (EPSPs). When two glutamate molecules bind to an AMPA receptor, the protein channel undergoes a conformational change that allows sodium and potassium ions to move along their electrochemical gradients. Sodium ions move into the cell and potassium ions move out simultaneously, so the voltage change is approximately half way between the equilibrium potentials of both ions. The result is a depolarision of a few millivolts.
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N-methyl-D-aspartate is a pharmacological agonist of one type of glutamate receptor, which is named NMDARs after this chemical.
The NMDA receptor is ligand-gated AND voltage-gated: it binds glutamate and glycine, but the size of the current flowing into the cell depends crucially on the transmembrane potential.
The dependence on the ongoing membrane potential is dependent on the fact that a magnesium ion blocks the entry of sodium and calcium through the channel at the normal resting potential. Sometimes this is known as open channel block.
However, when the membrane is depolarised, e.g. by the action of glutamate on AMPA receptors, the magnesium ion dissociates from the channel protein, and allows the influx of sodium and calcium.
When the membrane potential returns to its normal level, magnesium again binds to the channel and blocks entry of sodium and calium ions, even when glutamate is bound to the receptor.
NMDA antagonists include Ketamine, Pheylcyclidine and Nitrous Oxide (laughing gas). |
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The NMDA receptor is a complex ion channel that is ligand gated and voltage gated. The binding of magnesium ions at the normal resting potential prevents entry of sodium and calcium, even if glutamate is bound to the receptor. When the membrane is sufficiently depolarised, Mg2+ is released from its binding site and strong currents flow through the pore.
Note that zinc, glycine, polyamines and PCP also interact with the receptor. PCP (phencyclidine) is an NMDA receptor anatagonist. |
Within the cerebral cortex, repeated activation of NMDA receptors can modify the shape of dendritic spine synapses, and can alter the strength of the synaptic event. This is believed to play an important role in Long Term Potentiation (LTP), a phenomenon thought to be part of the process of neural learning and the laying down of memories.
One consequence of calcium entry to dendritic spines through NMDARs is the activation of (a) calmodulin kinase which plays a part in the induction of new AMPA receptors, and (b) the production of a retrograde messenger, possibly nitic oxide (NO), that can modulate release of transmitters by the presynaptic terminal. |
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The metabotropic glutamate receptors, or mGluRs, bind with glutamate, but instead of causing ion movements across the cell membrane, they activate a biochemical cascade that makes modifications to other proteins, including ion channels. These changes can lead to changes in synaptic strength and excitability, including the modulation of post-synaptic responses and presynaptic inhibition.
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Kainate receptors produce small slow depolarisations of post-synaptic neurones.
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