Lecture 9 - Transmitter Systems I Flashcards
What coagonist is needed for NMDA receptors to function properly?
Glycine
What are the 3 groups of biogenic amine neuromodulators?
Catecholamines, Indoleamine, & Imidazoleamine
How many and which subunits are ionotropic GABA receptors made of?
Ionotropic GABA receptors have a pentameric (5 subunit) assembly of 2α:2β:γ.
What is a common medical use of atropine? How does it work?
Atropine is a muscarinic antagonist. It inhibits muscarinic receptors in the eye and will result in pupil dilation. It is used for different ophthalmological procedures where pupil dilation is necessary.
Which type of glutamatergic ionotropic receptor is responsible for the majority of fast excitation?
AMPA
True or False?:
Histamine has 4 ionotropic receptors.
False
Histamine has 4 metabotropic receptors.
What are the three classes of glutamate ionotropic receptors?
AMPA, NMDA, & Kainate
True or False?:
Norepinephrine’s function in the CNS is not well understood because it has less wide-spread projections in the brain, but it has strong effects on the periphery.
False
Epinephrine’s function in the CNS is not well understood because it has less wide-spread projections in the brain, but it has strong effects on the periphery.
True or False?:
AMPA receptors act as co-incidence detectors during synaptic plasticity and act as a critical source of calcium.
False
NMDA receptors act as co-incidence detectors during synaptic plasticity and act as a critical source of calcium.
Which type of biogenic amine neuromodulator is serotonin (5-HT)?
Indoleamine
Which enzyme degrades acetylcholine?
Acetylcholinesterase
True or False?:
Glutamate is used in the brain while acetylcholine is used in the neuromuscular junction in vertebrates. This is flipped in invertebrates.
True
How would an I-V curve comparing NMDA receptors in the presence of glutamate and magnesium and NMDA receptors in the presence of glutamate without magnesium look?
How many transmembrane domains do ionotropic GABA subunits have?
4
What makes an NMDA receptor a co-incidence detector? What intracellular change indicates co-incidence?
NMDA receptors require two conditions to be met in order to open. Firstly, the presynaptic side must be active and releasing glutamate and the postsynaptic side must also be active and depolarized. As such, NMDA receptors allow you to detect when both the presynaptic and postsynaptic cells are active at the same time or within a short period of time (co-incidence). Since NMDA receptors are the only glutamatergic receptor that can pass calcium, a change in the internal calcium concentration is a marker for co-incidence.
Is GABA excitatory or inhibitory?
Inhibitory
True or False?:
Muscarinic receptors mediate most central effects of acetylcholine, as well as activation of the parasympathetic system.
True
What happens if magnesium enters the pore of a NMDA receptor? How is this dealt with?
When magnesium enters the pore of an NMDA receptor, it blocks the channel. (The positive ion is attracted to the negative interior of the cell.) The ion stays there until post-synaptic depolarization cause the ion to unblock the channel (because the negative charge becomes weaker), allowing current flow and calcium entry.
What are the two categories and five different dopamine receptors?
D1-Like (D1, D5) and D2-Like (D2, D3, D4)
True or False?:
ATP has both ionotropic and metabotropic receptors while adenosine has only metabotropic receptors.
True
Where in a GABAA repector does GABA bind?
GABA binds at a α-β interface.
Which type of glutamatergic ionotropic receptors contributes most to temporal summation? Why?
Kainate receptors contribute most to temporal summation because they have small amplitudes but long durations.
How do excitatory postsynaptic currents differ between AMPA and NMDA receptors?
AMPA receptors open very fast with a high amplitude but also close very fast. NMDA receptors open slower with a lower amplitude but stay open for longer.
True or False?:
AMPA and kainate receptors are non-specific cation channels while NMDA receptors can also flux calcium.
True
Which major neurotransmitter only has one subtype of receptor? What is that type?
Glycine only has ionotropic receptors.
True or False?:
Vesicular transporters are identical to those on the plasma membrane.
False
Vesicular membrane transporters differ from those on the plasma membrane.
What does benzodiazepine do?
Benzodiazepine binds to ionotropic GABA receptors between the β and γ subunits.
What are the 3 major types of catecholamines?
Dopamine, Norepinephrine, & Epinephrine
What binds to A1 autoreceptors instead of adenosine and blocks them?
Caffeine
What is the structure of nAChRs in the NMJ?
2α:β:ε:δ
Is glutamate excitatory or inhibitory?
Excitatory
What does serotonin do in the brain?
Serotonin regulates sleep/wakefulness, mood, anxiety, and food intake.
What is the name of the ionotropic serotonergic receptors? What are their characteristics?
The ionotropic serotonergic receptors are the 5-HT3A-E receptors. They are excitatory, pentomeric, and related to nAChR.
What would happen if you block acetylcholinesterase in a vertebrate?
The organism would die because acetylcholine would not be degraded and all muscles would be constantly activated.
How many transmembrane domains do muscarinic receptors have?
7
Where is histamine made in the brain?
Tuberomammillary Nucleus of Hypothalamus
True or False?:
Ionotropic receptors are typically excitatory or inhibitory while metabotropic receptors are typically modulatory.
True
True or False?:
Catecholamines only have ionotropic receptors.
False
Catecholamines only have metabotropic receptors.
True or False?:
Modulatory neurotransmitters are typically found in small clear vesicles so that they can rapidly be released while excitatory and inhibitory neurotransmitters are typically found in large dense-core vesicles that will have a slower release.
False
Excitatory and inhibitory neurotransmitters are typically found in small clear vesicles so that they can rapidly be released while modulatory neurotransmitters are typically found in large dense-core vesicles that will have a slower release.
What are the steps of the biosynthetic pathway for the catecholamine neurotransmitters (including enzymes)?
Tyrosine → DOPA via Tyrosine Hydroxylase
DOPA → Dopamine via DOPA Decarboxylase
Dopamine → Norepinephrine via Dopamine-β-Hydroxylase
Norepinephrine → Epinephrine via Phenylethanolamine-N-Methyl-Transferase (PNMT)
Where is serotonin made in the brain?
Raphe Nuclei
What is the structure of nAChRs in the CNS?
3α:2β
What are the two parts of the brain in which dopamine is produced? Which is each responsible for?
Substantia Nigra - Dopamine from here is essential for the initiation of voluntary movements and supressing unwanted movements. Breakdown of this area is responsible for Parkinson’s. (Contributes to motion.)
Ventral Tegmental Area - Dopamine from here is involved in reward pathways. Overactivation of this area is thought to be linked to addictions. (Contributes to motivation.)
What are the three types of postsynaptic effects of receptors?
Excitatory, Inhibitory, Modulatory
Why does GABA act as an excitatory neurotransmitter in immature neurons? How does this change through development?
In early development, neurons express a lot of the NKCC1 membrane protein, which pumps chloride into the cell. When GABAA receptors open, chloride flows out of the cell instead of into the cell, resulting in a depolarization. Through development, more of the KCC2 membrane protein is expressed which pumps chloride out of the cell. As the membrane proteins change, the chloride reversal potential decreases. When it gets below the threshold, GABA causes shunting inhibition instead of excitation. When it gets below the resting potential, it causes regular inhibition.
Where is norepinephrine made in the brain?
Locus Coeruleus
Is acetylcholine excitatory or inhibitory?
Excitatory
What do the transmembrane domains of muscarinic receptors create?
Unlike nicotinic receptors, muscarinic receptors don’t create a pore through the membrane. Rather, they create a binding pocket for ACh.
What is the rate limiting step of the biosynthetic pathway for the catecholamine neurotransmitters?
Tyrosine → DOPA via Tyrosine Hydroxylase
Where is epinephrine made in the brain?
Medullary Epinephrine Neurons
What does histamine do in the brain?
Histamine is involved in arousal/wakefulness.
Where is the G-protein binding site on the muscarinic receptors?
On the Intracellular C-Terminal
True or False?:
AMPARs have an amino-terminal domain and ligand-binding domain on the inside of the cell and a carboxyl-terminal domain on the outside of the cell.
False
AMPARs have an amino-terminal domain and ligand-binding domain on the outside of the cell and a carboxyl-terminal domain on the inside of the cell.
What are the steps of the biosynthetic pathway for serotonin (including enzymes)?
Tryptophan → 5-Hydroxytryptophan via Tryptophan-5-Hydroxylase
5-Hydroxytryptophan → Serotonin (5-Hydroxytryptamine) via Aromatic L-Amino Acid Decarboxylase
What two molecules combine to make acetylcholine? Where does the cell get them from?
Acetylcholine is made from acetyl CoA and choline. Acetyl CoA is an intermediate of cellular respiration (product of pyruvate oxidation) while choline is obtained through recycling (pumped back in from the synaptic cleft).
True or False?:
There is debate as to whether or not aspartate is a excitatory neurotransmitter.
True
True or False?:
There are 4 different α nACh and 10 different β nACh domains.
False
There are 10 different α nACh and 4 different β nACh domains.
True or False?:
Muscarinic receptors predominate at the NMJ and in the sympathetic ganglia, but are also found in the CNS.
False
Nicotinic receptors predominate at the NMJ and in the sympathetic ganglia, but are also found in the CNS.
True or False?:
GABA is synthesized out of glutamate by glutamic acid decarboxylase.
True
What does norepinephrine do in the brain?
Norepinephrine regulates a number of functions like sleep/wakefulness, attention, eating, mood, and memory-retrieval. It also signals sympathetic activation.
What are ionotropic cholinergic receptors activated by? What are they therefore called?
Ionotropic cholinergic receptors are activated by nicotine. As such, they are called nicotinic receptors (nACh).
True or False?:
ATP is often co-released with other transmitters,
True
Which type of biogenic amine neuromodulator is histamine?
Imidazoleamine
How do excitatory postsynaptic currents differ between AMPA and kainate receptors?
AMPA receptors open very fast with a high amplitude but also close very fast. Kainate receptors open at the same rate, but have a lower amplitude and also stay open for much longer.
How do nAChRs and AMPARs differ?
nAChRs have four transmembrane helices and have both the N and C terminals outside the cell. AMPARs have three transmembrane helices plus a pore loop and have the N terminal outside the cell and the C terminal inside the cell.
Theoretically, how many vesicular transporters are needed to fill a vesicle?
One
Is glycine excitatory or inhibitory?
Inhibitory
What is ATP quickly broken down to?
Adenosine
True or False?:
There are receptors for both ATP (P1 or A type) and adenosine (P2 type).
False
There are receptors for both ATP (P2 type) and adenosine (P1 or A type).
