AMPA receptor · Grey Matter

The AMPA receptor is the glutamate-gated ion channel that carries nearly all fast excitation in the brain: when glutamate binds it opens within a millisecond, lets sodium in, and depolarises the receiving neuron for a few milliseconds.

AMPA receptor. The AMPA receptor is the glutamate-gated ion channel that carries nearly all fast excitation in the brain: when glutamate binds it opens within a millisecond, lets sodium in, and depolarises the receiving neuron for a few milliseconds.

It is built from four subunits (GluA1 to GluA4) around a pore. Glutamate binding opens it almost at once, and the channel closes again quickly, both because glutamate unbinds and is cleared and because the receptor desensitises if glutamate lingers; the resulting current typically decays with a time constant of one to a few milliseconds. Most AMPA receptors in the adult brain contain the GluA2 subunit, which makes them impermeable to calcium; those lacking it pass calcium as well.

The number of AMPA receptors at a synapse is the main measure of its strength. Long-term potentiation adds receptors and makes them conduct better; long-term depression removes them by endocytosis.

It is the partner that unlocks the NMDA receptor. The depolarisation produced by AMPA currents is what expels the magnesium block from the NMDA receptor next to it.

Drugs that block AMPA receptors (perampanel) reduce seizures, which shows how much of the brain's excitability rides on this one channel.

The AMPA receptor is the brain's default excitatory messenger.

Its speed makes it carry the content of a signal, and its count at each synapse is the weight that learning adjusts.

Questions: How does the NMDA receptor detect that two neurons fired together? The NMDA receptor needs two conditions at once: glutamate bound, which means the presynaptic cell has just released, and a depolarised membrane, which means the postsynaptic cell is active. At resting voltage a magnesium ion from outside the cell sits in the pore and blocks it even when glutamate is bound; depolarisation, usually from the AMPA receptors beside it or from a spike back-propagating into the dendrite, pushes the magnesium out. Only then does the channel pass current, including calcium. Glutamate alone opens just the AMPA receptors, depolarisation alone opens nothing, and the two together let in the calcium that signals plasticity. What physically changes at a synapse that has been potentiated? Mostly the postsynaptic side gains AMPA receptors: more of them are inserted and held at the synapse, and existing ones are phosphorylated so each conducts more, so one vesicle of glutamate now produces a larger current. Within minutes to hours the spine head grows, its scaffold of proteins enlarges to hold the new receptors, and in late LTP new proteins are made to keep the change. Some forms also raise the probability of release on the presynaptic side. Synapses that had NMDA receptors but almost no AMPA receptors (silent synapses) can be switched on this way, which is common in development. Why is the AMPA current over within a few milliseconds of glutamate release? Glutamate in the cleft reaches a high concentration for only about a millisecond before it diffuses away and is taken up by transporters, and AMPA receptors bind it with low affinity, so they let go quickly. Those that stay bound close anyway within milliseconds by desensitising. The current therefore decays with a time constant of roughly one to a few milliseconds, and below a millisecond at some fast synapses onto interneurons. The brevity is what lets AMPA synapses carry precise timing, while the slower NMDA current beside them integrates over a hundred milliseconds or so.