Neurobiology 5 Flashcards
Describe the structure of a C-loop receptor?
Pentamers with 5 subunits, where there are Cys-Cys disulfide bridges in the N-terminal loop region.
List 5 ligands for C-loop receptors.
Acetylcholine, serotonin, GABA, glycine and histidine (insects).
Describe the structure of pore loop receptors.
Tetramers, where 4 subunits are assembled to form a transmembrane channel.
Which receptor is typically larger - C loop or P loop?
P loop receptors.
Describe an excitatory post-synaptic potential.
Sum to give an action potential once a certain threshold is reached.
Describe an inhibitory post-synaptic potential.
Occurs as a result of potassium leaving the neuron and chloride ions entering the neuron.
Describe the ‘integrate and fire’ model.
An excitatory and inhibitory post synaptic signal are added together to decide whether or not an action potential is fired..
What is the inhibitory receptor in the mammalian brain?
GABA receptor.
Describe a GABA receptor.
GABA gated chloride channel - a C loop pentameric receptor.
What is GABA derived from?
The amino acid glutamate
Give 2 examples of excitatory receptors.
Glutamate/AMPA receptor.
Nicotinic acetylcholine receptor.
Describe a Glutamate/AMPA receptor.
Ligand gated Na+ and K+ channel (predominantly Na+).
What type of receptor is the nicotinic acetylcholine receptor?
C-loop receptor - ligand gated sodium channel.
What happens when ACh binds to the ACh receptor in muscle cells?
The channel opens and sodium ions move down their gradient and depolarise the muscle cell.
This AP causes Ca influx into the muscle causing actin-myosin muscle movement.
What happens when you block ACh receptors?
Paralysis.
What animal was used to determine the structure of Ache receptors?
An electric fish - torpedo marmorata, which specialises in generating a large electrical voltage that paralyses its prey.
Why was the Torpedo fish selected for the structural determination of Ach receptors?
The muscle is packed full of acetylcholine receptors, which are almost crystalline in their native state – high quantity allows for high electrical conduction
What is the structure of Ach receptor?
Five subunits come together to form a channel - alpha, beta, gamma, delta (often 2 alpha).
What type of receptor is the GABA receptor?
C-loop receptor - ligand gated chloride channel.
Is GABA a symmetric synapse?
Yes
What is the post-synaptic density like in inhibitory synapses?
Very sparse - there are not many proteins.
What must the pre-synaptic neuron express to be a GABAergic synapses?
Glutamate decarboxylase and a GABA vesicular transporter.
What are the three different types of GABA receptors that GABAergic synapses use?
GABA(A), GABA(B) and GABA(C).
What happens when GABA binds to a GABA(A) receptor?
The channel opens and chloride ions move down their electrochemical gradient - hyperpolarising the motor neuron.
Why does the GABA receptor not bind Ach?
It contains different amino acids in its selectivity filter - making it specific to GABA. - distance between carbonyls and GABA matches hydration shell
Describe the composition of GABA.
A four-carbon carboxylic acid, with an amino group at gamma carbon
What is the function of glutamate decarboxylase?
Removes the carboxyl group from glutamate to form GABA.
How many isoforms does glutamate decarboxylase exist in?
2
How do glial cells involved in the reproduction of GABA?
Convert glutamate to glutamine, by glutamate synthase. Glutamine can then be converted into glutamate and then into GABA in neurons.
Give an example of a drug that targets GABA(A) receptor?
Anti-convulsants (barbiturates) - used to treat epilepsy.
How do these drugs affect the GABA receptor?
They modulate it - allowing it remain open longer/closing it.
Where do barbiturates bind to on the GABA receptor?
Between alpha and beta subunit.
What type of receptor is the AMPA glutamate receptor?
Pore-loop receptor - ligand gated sodium channel.
What is the main excitatory neurotransmitter found in mammalian cells?
Glutamate.
What cellular process does come from?
The krebs cycle.
What happens when glutamate binds to its receptor?
Sodium ions influx down their gradient and depolarise the neuron (k+ ions also efflux but Na ions dominate so there is an excitatory response).
Describe the structure of AMPA glutamate receptor.
Tetrameric
4 subunits - GluA1, 2, 3 and 4.
Typically heteromers.
Ionotrophic
Define an ionotrophic receptor.
Receptors in which the ligand binding site is an integral part of the receptor molecule.
Define a Mechanoreceptors.
Receptors that specialise in sensing mechanical forces.
Name the domains of the ionotropic Glutamate receptor (iGluR).
Large N terminal domain.
Ligand binding domain.
Long C terminal domain.
How are the domains in iGluR arranged?
The subunit strands twist around each other to form the glutamate receptor structure.
Describe the ligand binding domain of iGluR.
Clam-like structure - when it binds glutamate it closes and causes a conformation change in the P loop.
What happens if the knee is tapped?
knee jerk reflex occurs - activates stretch receptors, causing an influx of sodium ions into the sensory neuron.
