Ionotropic Receptors

What are the families of ionotropic receptors?

* Pentameric: (cys-loo), pentamer, Nicotinic ACh receptors and GABA receptors
* Glutamate: tetramer receptors, NMDA and AMPA receptors
* Trimeric: timer receptors, ATP receptors
* TRP: tetramer but not like glutamate. Popular in the pain receptors and sensory stimuli

Which site of Acetycholine receptos contains the binding site? How many acetylcholin need to bind in order for the receptor to work?

* the alpha subunit contains the binding site
* the acetycholine receptor needs at leat 2 acetycholine to bind to the receptor

What are two points about ligand binding?

* the binding of a ligand to a receptor is probailistic. This, binding frequency depends on the concentration of the ligand.
* the amount of time a ligand spends bounds to a receptor binding site varies by ligand (Kd)

Dissociation Constant (Kd)

the concentration of a ligand at which 50% of receptors are occupied (i.e. have a ligan bound to them)

What is an agonist?

a compound that elicits the same biological effect(s) as the endogenous (naturally-occuring) ligand when it binds ot a receptor. (i.e. ACh and Nicotine→ nictotine is the nAChR agonist)

What is an antagonist?

A compound that reduces or eliminates the effect of an agonist when bound to a receptor.

What is a competitive antagonist?

binds to the same site as an agonist (orthosteric binding) but does not activate the receptor. This reduces or prevents activation of the channel bu an agonist.

What is a non-competitive antagonist?

binds to the receptor at a different site from an agonist (allosteric binding) but prevents or reduces activation of the receptor. REferred to as a NAM (negative allosteric modulator)

Reversible antagonist

binds non-covalently to the receptor, so can come off the receptor by “washing off” (i.e. tubocurarine)

What is an irreveersible antagonist?

binds covalently to the receptor, so cannot be displaced bu either competing ligands or “washing off”

i.e. alpha-bungarotoxin

What are the two types of GABA receptors?

* GABA-B are metabotropic receptors
* GABA-A are in the pentameric receptor family with nAChRs; they are ligand-gated chloride channels
* chloride channels at resting potential→ chloride always wants to move into the cell and thus, hyperpolarize the cell.

Glycine receptors (GlyRs)

* inhibitory neurotransmitter (glycine) like GABA-A receptors
* also is a chloride channel
* the gating is much quicker and the channels desensitizes quicker.
* GABA-A is much slower to desensitize

What is the ionotropic glutamate receptor structure?

* tetramet
* NMDA and AMPA and Kainate receptors
* there are four components: Amino-terminal domains, ligand binding domains, transmmebrane domains, and carboxy-terminal domains (note the significant lack of dipping into the cytoplasm from teh receptor)

Non-NMDA glutamate receptors:

* AMPA and kianate
* low conductance
* fast gating speeds
* ion permeability just to Na+ and K+

NMDA receptors

* high conductance
* slow gating speed
* ion permeability to Na+, K+ and Ca++
* there is an Mg++ block in the pore of the channel and thus, blocks calcium conductance

Magnesium block of NMDA glutamate receptors

* at resting membrane potential, mg is in the way so there is no influx of calcium
* inorder to have conductance of calcium→ the cell must be depolarized in order to relieve the magnesium block
* then glutamate binds, the channel opens and allows Calcium, sodium in and potassium out and then magnesium block returns when the cell returns to rest,
* NMDA receptors are coincident indicators
* need to release two glutamate in order to open teh NMDA receptor