NEUROTRANSMITTER RECEPTORS
Receptors for Amino-acid Neurotransmitters
Receptors for each of the amino acid neurotransmitters can either;
1. Directly open an ion channel (ionotropic)
2. Couple to a G-protein (G-protein coupled receptor; GPCR) except for glycine.
There is no known GPCR for glycine
All of glycine’s effects are mediated through an ion channel permeable to Chloride ions.
A. Glutamate Receptors
There are at least three distinct types of glutamate receptors.
Two are ionotropic since glutamate binding directly opens an ion channel and the other is
GPCR, producing alterations in intracellular messengers.
The three distinct types of glutamate receptors have been characterized by using agonists that
specifically activate each type;
1. NMDA (N-Methyl-D-Aspartate, a synthetic compound that acts as an agonist for this
particular glutamate receptor subtype)
2. Non-NMDA (also known as kainite/AMPA receptors since these agonists activate this
receptor subtype)
3. G-protein coupled glutamate receptor
Ionotropic Glutamate receptors open channels that cause the cell to depolarize and are
therefore excitatory
Glutamate opens receptors, selectively permeable to cations (Na+, K+ and Ca2+)
Opening of Non-NMDA receptors causes the majority of the excitatory postsynaptic
potentials (EPSPs) in the nervous system.
This receptor is mainly permeable to Na+ and K+.
The structure of non-NMDA receptors loosely resemble the Nicotinic Acetylcholine (Ach)
receptor although glutamate receptors have some unique features
NMDA receptors are unique in the nervous system and exhibit two important characteristics;
1. First, they have a high permeability to Ca 2+ (although they are also permeable to Na + and
K+) and when they open significant increase in the level of Ca 2+ can be detected in the
1
, neuron. Increased levels of Ca2+ activate wide variety of enzyme systems that alter both
the short and long-term response of the neurons. Glycine which is normally always
present in the extracellular space is also required for the NMDA receptor to open.
2. Second, NMDA receptors require both ligand binding and membrane depolarization to
open. The channel associated with the NMDA receptor binds Mg2+, stopping ions from
flowing through the channel. Mg2+ can be displaced from the channel by depolarizing the
membrane. This unique property imparts to the receptor the capacity to sense the
membrane potential and open only when the neuron is depolarized. The ability to sense
presynaptic activity (through the binding of released glutamate) and postsynaptic activity
(through sensing membrane potential) means the NMDA receptor associates the two
activities. This property (Associativity) fulfills one of the central criteria for a molecule
involved in learning
B. GABA Receptors
Some GABA receptors are ionotropic receptors which are selectively permeable to Cl-.
When they open, they cause the neuron to hyperpolarize and therefore drive the
membrane potential away from the threshold for firing an action potential.
Some GABA receptors also binds to and activates GPCR.
The ionotropic and G-protein coupled GABA receptors are referred to as GABAA and
GABAB respectively.
Some of the main features of GABA receptors are as follows;
2
Receptors for Amino-acid Neurotransmitters
Receptors for each of the amino acid neurotransmitters can either;
1. Directly open an ion channel (ionotropic)
2. Couple to a G-protein (G-protein coupled receptor; GPCR) except for glycine.
There is no known GPCR for glycine
All of glycine’s effects are mediated through an ion channel permeable to Chloride ions.
A. Glutamate Receptors
There are at least three distinct types of glutamate receptors.
Two are ionotropic since glutamate binding directly opens an ion channel and the other is
GPCR, producing alterations in intracellular messengers.
The three distinct types of glutamate receptors have been characterized by using agonists that
specifically activate each type;
1. NMDA (N-Methyl-D-Aspartate, a synthetic compound that acts as an agonist for this
particular glutamate receptor subtype)
2. Non-NMDA (also known as kainite/AMPA receptors since these agonists activate this
receptor subtype)
3. G-protein coupled glutamate receptor
Ionotropic Glutamate receptors open channels that cause the cell to depolarize and are
therefore excitatory
Glutamate opens receptors, selectively permeable to cations (Na+, K+ and Ca2+)
Opening of Non-NMDA receptors causes the majority of the excitatory postsynaptic
potentials (EPSPs) in the nervous system.
This receptor is mainly permeable to Na+ and K+.
The structure of non-NMDA receptors loosely resemble the Nicotinic Acetylcholine (Ach)
receptor although glutamate receptors have some unique features
NMDA receptors are unique in the nervous system and exhibit two important characteristics;
1. First, they have a high permeability to Ca 2+ (although they are also permeable to Na + and
K+) and when they open significant increase in the level of Ca 2+ can be detected in the
1
, neuron. Increased levels of Ca2+ activate wide variety of enzyme systems that alter both
the short and long-term response of the neurons. Glycine which is normally always
present in the extracellular space is also required for the NMDA receptor to open.
2. Second, NMDA receptors require both ligand binding and membrane depolarization to
open. The channel associated with the NMDA receptor binds Mg2+, stopping ions from
flowing through the channel. Mg2+ can be displaced from the channel by depolarizing the
membrane. This unique property imparts to the receptor the capacity to sense the
membrane potential and open only when the neuron is depolarized. The ability to sense
presynaptic activity (through the binding of released glutamate) and postsynaptic activity
(through sensing membrane potential) means the NMDA receptor associates the two
activities. This property (Associativity) fulfills one of the central criteria for a molecule
involved in learning
B. GABA Receptors
Some GABA receptors are ionotropic receptors which are selectively permeable to Cl-.
When they open, they cause the neuron to hyperpolarize and therefore drive the
membrane potential away from the threshold for firing an action potential.
Some GABA receptors also binds to and activates GPCR.
The ionotropic and G-protein coupled GABA receptors are referred to as GABAA and
GABAB respectively.
Some of the main features of GABA receptors are as follows;
2
