Neurotransmission 2 - Kenyon Flashcards
How many families of neurotransmitter receptors are there? What are they called?
4 families
- Ionotropic ligand gated ion channels
- Tyrosine kinase enzyme-linked receptors
- G-protein coupled receptors (GPCRs)
- Intracellular receptors for unconvential neurotransmitters.
What is the difference between ionotropic and inotropic?
Ionotropic: single transmembrane protein binding a neurotransmitter that acts as the channel for cation movement.
Inotropic: ability of muscle to generate force at a given length.
Are ionotropic receptors made from a specific set of subunits or a combination?
A combination of many!
What the ionotropic receptors for glutamate? (3)
- AMPA
- NMDA
- Kainate
Do GPCRs directly or indirectly influence opening/closing of ion channels?
Both!
Are GPCRs 1TM or 7TM?
1TM
Can GPCRs elicit multiple intracellular effects?
yes!
What is an orphan receptor?
A 7TM receptor that looks like a metabotropic receptor but the neurotranmisster is unknown.
Describe the function of a metabotropic (GPCR) receptor?
- Nuerotransmitter binds.
- g-protein activated
- G protein subunits or intracellular messengers modulate ion channels
- Ions flow across membrane
- Ion channel opens.
Describe the function of an ionotropic receptor?
- neurotransmitter binds
- Channel opens
- Ions flow across the membrane.
Can you form an ionotropic receptor by mixing and matching subunits?
Yes! Can make hundreds of receptors from subunit pool.
Are there many or few metabotropic receptors?
Few, <10
Do ionotropic receptors have a limited or extensive set of intracellular responses?
What is the primary effect?
Limited response, mostly changes membrane potential.
Allowing (blank) ions through an ionotropic receptor will increase the number of intracellular effects?
Calcium!
Do metabotropic receptors have limited or extensive intracellular effects?
“UNLIMITED” biochemical responses!
GPCR->signaling cascade systems
Activation of a (blank) receptor will change a neuron’s likelihood of firing an action potential
Metabotropic
Why does Ca influx alter the function of ionotropic receptors?
Calcium is central in all vitally controlled cell processess–death, growth, continuation of life, etc.
Do tyrosine kinase enzyme linked receptors directly or indirectly open and close ion channels?
Indirectly!
Enzyme-LINKED
The (blank) enzyme involved in nitric oxide synthesis dependent on (blank) ions.
NO synthase
Calcium
What are the four general groups of small molecule neurotransmitters?
- ACh
- Amino acids
- Biogenic amines
- Purines
What are the amino acid NT’s? (4)
- Glutamate
- Aspartate
- GABA
- Glycine
What are the biogenic amines (3)?
- Catecholemines (NEpi, Epi)
- Serotonin (5-HT)
- Histamine
What are the purines (4)?
ATP, ADP, AMP, Adenosine
Gastrin releasing peptide is involved in remembering (blank).
Fearful situations
What is the general postsynaptic effect of ACh?
Excitatory
What is the general postsynaptic effect of glutamate?
Excitatory
What is the general postsynaptic effect of GABA?
Inhibitory
What is the general postsynaptic effect of glycine?
Inhibitory
What is the general postsynaptic effect of catecholemines?
Excitatoryo
What are the precursors to ACh?
Choline, acetyl CoA
what is the rate limiting step in ACh synth?
CAT
How is AcH removed?
AChEase
How are glutamate, GABA, glycine removed?
Transporters
How are catecholemines removed?
Transporters and MAO
What is the general postsynaptic effect of 5-Ht?
Excitatory
What is the general postsynaptic effect of Histamine?
Excitatory
What is the general postsynaptic effect of ATP?
Excitatory
What is the general postsynaptic effect of neuropeptides?
Excitatory and inhibitory
What is the precursor to 5-Ht?
Tryptophan
What is the rate limiting step in 5-HT synth?
tryptophan hydroxylase
How is 5-Ht removed?
Transporters and MAO
How is histamine removed?
Transporters
What is the precursor to ATP?
ADP
How is ATP removed?
Hydrolysis to ADP and adenosine
What are the precursors to neuropeptides?
amino acids
How are neuropeptides removed?
proteases
What are the precursors to endocannabinoids?
Membrane lipids
what is the rate limiting step for endocannibinoids?
enzymatic mod of lipids
what is the precursor for NO?
ARRRRginine!
What is the rate limiting step for NO? What ion does it require?
NO synthase, requires Ca
How is NO removed?
Spontaneous oxidation
At what types of synapes do you find ACh? (3)
- Neuromuscular junction
- Preganglionic autonomic ganglia
- Post-ganglionic parasympathetic neurons
How is choline recovered from the broken down ACH in the synaptic cleft?
via Na/choline transporter
What are the two general classes of ionotropic nicotinic ACH receptor (nAChR)?
- Muscle nAChR
2. Neuronal nAChR
How many types of muscle nAChR are there?
2: one adult and one fetal
Are there multiple or few neuronal nAChR?
ZILLIONS
How many subunits are required to form an nAChR?
4-5
ACh, nicotine, curare, and bungaratoxin, d-tubocurarine, and succinylcholine bind at which subunit on muscle nAChR?
alpha 1
Does hexamethonium bind at muscle or neuronal nAChR?
Nueronal
Are muscarinic AChR metabotropic or ionotropic?
Metabotropic
In what types of tissue do you find muscarinic AChR? (3)
- Neurons
- Smooth muscle
- Cardiac muscle
Do muscarinic AChR’s mediate normal neuromuscular transmission?
NO
What is the priniciple fast excitatory neurotransmitter?
Glutamate
What transporter collects glutamate?
EAAT’s.
What cell type actively collects glutamate?
Glial cells
What are the three artificial agonists?
- AMPA
- NMDA
- Kainate
Do all artificial agonists pass cations?
YES
Do all artificial agonists pass Ca?
only some
Do all artificial agonists mediate EPSPs?
YES
Different receptors show different kinetics?
Most certainly
What ions does the NMDA pore allow to pass? (3)
(Na, K, and Ca)
What change to cell polarization will NDMA receptors have
they can depolarize the cell and and activate Ca processes.
What ion blocks the NMDA channel?
MG
Is activation of the NMDA receptor sufficient for alteration of resting potential?
NO, that Mg messes everything up
Describe the process of NMDA receptor activation and subsequent cellular responses?
- Glutamate binds NMDA, but nothing happens yet.
- AMPA generally doesn’t let calcium in. However, binding glutamate to NMDA lets AMPA let Na in
- Cell depolarizes from NA influx
- Ca comes in through NMDA
- Ca in the cell can now go do its thang
AMPA depolarization leads to (blank) potentiation
Long-term
What effect does AMPA have on EPSP?
it makes them larger
where is there vesicle fusion during AMPA activation?
both pre and post synaptically
Is the power of a glutamate synapse adjustable?
Yes!
What changes does a tetanic stimultion have on EPSPs?
it makes them LARGER
The combo of (blank and blank) receptors is necessary for Ca entry.
NMDA
AMPA
Ca in the cell can cause long term (blank) or (blank)
potentiation
depression
What is the effect of high extracellular glutamate on nerve cells?
IT KILLS THEM
What ion precedes cell death via glutatmate/
Ca, blocks glutamate receptors
Are glutamate receptors metabotropic or ionotropic?
Metabotropic
What special neural cell type has glutamate receptors?
Astrocytes!
Which two GABA receptors are ionotropic? what ion do they mediate?
GABA A
GABA C
Chloride ions
what class of drug is a common ionotropic GABA agonist?
Benzo’s
What GABA receptor is metabotropic?
GABA B
do ionotropic GABA receptors effect EPSP or IPSP?
IPSP, they’re inhibitory!
What is the enzyme that pumps GABA into vesicles presynaptically?
VIATT: Vesicular inhibitory Amino Acid Transporter
The effects of alcohol are mediated by what neurotransmitter? The ionotropic or metabotropic variety?
GABA, ionotropic
Activation of the inhibitory neuron (that released GABA) stops the action potentials in the (blank)-synaptic neuron but does not (blank)-polarize the postsynaptic neuron. The action potentials stop because the depolarization to threshold is (blanked).
- post-synaptic
- hyperpolarize
- slowed
Glycine activates ionotropic (blank) ion channels
Cl
What blocks glycine receptors in the spinal cord?
Strychnine
What are the 5 biogenic amines?
- Dopamine
- NEpi
- Epi
- histamine
- serotonin
What does the presence of tyrosine hydroxylase indicate about a neuron?
THEY RELEASE THE CATECHOLEMINES
How is dopamine inactivated?
Na-dependent uptake (DAT)
What drug inhibits dopamine uptake?
COCAINE
What class of receptor are dopamine receptors?
Metabotropic
Dopaminergic neurons stem from what region of the brain?
originate in substantia nigra, continue to the corpus striatum (caudate and putamen)
What processes are dopamine involved in?
- Coordination of movement (PARKINSON)
- Motivation
- Reward
- Reinforcement
- Addiction
Where is NEpi released?
sympathetic post-ganglionic neurons
What inactivates Nepi?
NET; also transports dopamine
what inhibits NET?
Amphetamines, man!
What class of receptor are alpha and beta adrenergic receptors?
metabotropic
Noradrenergic neurons in locus coeruleus project to forebrain and cause (blank)
sleep wakefulness, attention, feeding.
Adrenergic neurons containing Epi are located in lower brainstem (medulla). They project to (blank) and (blank). The function is not clear.
hypothalamus and thalamus
what class of receptor is histamine?
metabotropic
Histamine is involved in what three processes?
- Allergic response
- Pain
- itch
Serotonin is important in:
- psych disorders
- pain (centrally and peripherally)
- GI tract
Prozac does what?
Selective serotonin reuptake inhibitor
5-HT3 class of receptors are metabo or ionotropic?
Ionotropic, nonselective cation channels
Purine transmission is important where?
Periphery (smooth muscle) Nervous system (mechanosensation and pain)
What enzyme creates a “soup” of purines?
extracellular ecto-5’ nucleotidases
Nueropeptide pre-propeptides are are targeted with a signal plexus that sends them where in the cell?
ER and Golgi
can neuropeptides travel to affect distant neurons?
YES
Are neuropeptides slow or fast? Short or long lasting?
SLOOOOOOWW AND LOOOOONG
Do endocannibinoids have brain pain control?
NO NO NO NO
What is considered a retrograde messenger?
NO