postsynaptic receptors - glutamate

What are the two main types of postsynaptic receptors?

Ionotropic receptors (ligand-gated ion channels) and metabotropic receptors (G protein-coupled receptors).

Describe ionotropic receptors.

Ionotropic receptors are ligand-gated ion channels that open in response to neurotransmitter binding, allowing ions to flow through, leading to a postsynaptic potential (PSP).

Describe metabotropic receptors.

Metabotropic receptors are G protein-coupled receptors that, upon neurotransmitter binding, activate G proteins which trigger intracellular signaling cascades, often amplifying the signal.

What determines whether a postsynaptic response is excitatory or inhibitory?

The type of ion the postsynaptic receptor is permeable to: cations (excitatory, depolarizing) or anions (inhibitory, hyperpolarizing).

What is the main excitatory neurotransmitter in the brain?

Glutamate.

List the three types of ionotropic glutamate receptors.

AMPA receptors, NMDA receptors, Kainate receptors.

What are the subunits for AMPA receptors?

GluA1-GluA4.

What are the subunits for NMDA receptors?

GluN1 and GluN2A-D.

What are the subunits for Kainate receptors?

GluK1-GluK5.

What is the general structure of ionotropic glutamate receptors?

Tetramers composed of four subunits, each with 3 transmembrane regions, an extracellular N-terminal tail, an intracellular C-terminal tail, an extracellular loop, and an M2 domain that forms the pore.

Which ionotropic glutamate receptor is highly permeable to calcium?

NMDA receptors.

Why are most AMPA receptors impermeable to calcium?

They contain the GluA2 subunit, which adds a positive charge to the pore area, making it impermeable to calcium.

What is the reversal potential for glutamate receptors?

Approximately 0 mV.

Why is glutamate receptor signaling always excitatory?

Because at resting membrane potential (-60 mV), the driving force causes an influx of positive ions (Na+, Ca2+), leading to depolarization.

Outline the process of glutamate signaling.

1. Glutamate is released from the presynaptic neuron.

2. Binds to AMPA receptors on the postsynaptic membrane.

3. Opens ion channels, allowing Na+ and K+ to flow.

4. At resting potential, Na+ influx causes depolarization (EPSP).

5. EPSP travels to the axon initial segment.

6. If sufficient, triggers an action potential.

What is EPSP summation?

Amount of neurotransmitter released, size and shape of the postsynaptic neuron, driving force, presence of inhibitory neurotransmitters (GABA, glycine), location of the synapse, number of AMPA receptors, glutamate receptor subtype, number of synaptic inputs.

What is the unique feature of NMDA receptors that makes them coincidence detectors?

They require both glutamate binding and depolarization to remove the Mg2+ block, allowing ion flow.

What is the role of NMDA receptors in synaptic plasticity?

They allow Ca2+ influx, which activates signaling pathways crucial for memory formation and synaptic plasticity.

List the three groups of metabotropic glutamate receptors and their general effects.

Group I (mGluR1,5): Excitatory, postsynaptic

Group II (mGluR2,3): Inhibitory, presynaptic

Group III (mGluR4-8): Inhibitory, presynaptic.

What is the role of auxiliary subunits in AMPA receptors?

They are involved in cell surface trafficking and stabilization of AMPA receptors.

Explain the voltage dependence of NMDA receptors.

At resting membrane potential, Mg2+ blocks the NMDA receptor pore. Depolarization removes the Mg2+ block, allowing ion flow when glutamate is bound.