Neurotransmitters Flashcards
What are the 4 points that define a neurotransmitter?
Presence: must be produced and stored in the presynaptic terminal
Release: must be released from terminal upon pre-synaptic stimulation
Postsynaptic receptors: receptors that it can bind should be present on the post-synaptic membrane
Inactivation
Can you outline the steps from Neurotransmitter production and release beginning with synthesis?
Presynaptic:
- Synthesis of NT
- Storage
- Release of NT
Post-synaptic:
- NT interacts with receptor on post-synaptic membrane
- Removal of NT from synapse
Synthesis: Small-Molecule Neurotransmitters
- Small molecule NT are synthesized in the presynaptic terminal
- Enzymes to produce the NT are made in the cell body and transported down to the axon (slow)
- Precursors for NT are taken up in the terminal
- Occurs with small, clear vesicles
Synthesis: Neuropeptides
Synthesized on the rough ER located in the cell body
Precursor peptides are packaged in vesicle then transported by terminals via fast axonal transport
Mature peptides are synthesized by enzymes at the axon terminal–> cleave off into the active peptide portions
Storage: Types of Vesicles
Small Synaptic Vesicles:
- Classical NT’s
- Ach, Glutamate, GABA, Glycine
Large Dense Core Vessicles:
- Neuropeptides (generally)
- Dopamine, Norepinephrine
T of F: A single neuron can have both large dense core vesicles and small synaptic vesicles in the same neuron
True
Outline of NT production and release
- Synthesis and storage of NT
- AP arrives in terminal–> NA+ ion channels let Na+ in–> membrane potential changes
- Voltage gated CA2+ channels open–> allows Ca2+ inside–> mobilization of vesicles
- Increase of Ca2+ triggers the fusion of vesicles with presynaptic membrane
- NT released via exocytosis across synaptic cleft
Compare and contrast synthesis and storage of small molecule neurotransmitters and neuropeptides.
Neuropeptides:
- Synthesized on the rough ER located in the cell body
- Precursor peptides are packaged in vesicle then transported by terminals via fast axonal transport
- Mature peptides are synthesized by enzymes at the axon terminal–> cleave off into the active peptide portions
Small molecule NT:
- Small molecule NT are synthesized in the presynaptic terminal
- Enzymes to produce the NT are made in the cell body and transported down to the axon (slow)
- Precursors for NT are taken up in the terminal
- Occurs with small, clear vesicles
What are the two types of storage vesicles?
Small synaptic vesicles
- Ach, glutamate, GABA, glycine
Large dense core vesicles
- Neuropeptides, dopamine, NE
BOTH can be found in the same cell, AP determines if one or both are released
Release of Vesicles:
How do the vesicles differ with respect to the mechanism which stimulates them to dump their product?
Small Vesicles:
- Released with low stimulation
- Local increases in Ca2+ cause them to be released
- Preferential release due to low-frequency stimulation
Dense core vesicles:
- Released with high-frequency stimulation
- Dependent on general calcium levels
- High would ultimately cause the release of both
Large amount of Ca2+ = both vesicles released
Name 2 different types of receptors on the post synaptic membrane that a NT could bind to cause an effect.
How do they differ?
Ionotropic Receptors:
- Very fast
- Each receptor (multiple subunits) contains an ion channel @ center
- At rest= channel is closed
- NT binds = channel opens
- When the ligand leaves, the channel quickly closes
Metabotropic Receptors:
- Works more slowly than ionotropic receptors
- Long lasting
- DO NOT possess a channel or pore
- Have an NT binding site
- Causes a G-protein to be activated which signals a cascade, opening an ion channel or a second messenger
What are 3 ways that a neurotransmitter can be removed from a synapse?
Glial cells: Can reuptake the NT via transporters
Enzymatic degradation = in synapse & presynaptic terminal
(Binds to receptors, falls off and enzymes work to degrade the NT so the effect is not long lasting)
Pre-synaptic reuptake by transporters
How Is acetylcholine made?
What 2 components are used?
Amine– but not derived from an amino acid
Synthesis: Choline + Acetyl coA
Effect on Postsynaptic Cell:
- Found in neuromuscular junctions so ALWAYS excitatory
Ionotropic Receptors: Nicotinic are found in muscle (specifically skeleton)
Muscarinic: Found in the heart, smooth muscles of the brain
Brain- binds to metabotropic receptors in CNS
PNS: binds to ionotropic receptor
Removal: degradation by enzymes
For all 3 of these catecholamine neurotransmitters, name the two ways by which they are recycled (broadly speaking, not all the details, they are taken up by _____ and by ______)
Norepinephrine, dopamine, epinephrine
Synthesis requires tyrosine (rate limiting step is the supply of tyrosine and tyrosine hydroxylase to create the precursor for the NT)
Removal Is done by two enzymes (COMT, MAO)
COMT: Catechol-O-Methyltransferase
MAO: Monamine oxidase
Norepinephrine
Synthesis:
Tyrosine hydroxylase pre-cursor –> Dopamine–>
Dopa decarboxylase–> Dopamine–>
Dopamine beta-hydroxylase–> NE
Effects on postsynaptic cell: EPSP
Acts on metabotropic receptors (G-protein coupled)
Removal:
- Re-uptake via NET transporter
- Reuptake into presynaptic cell or surrounding glial cells via NET transporter
- Degraded by momoamine oxidase (MAO) or COMT inside cell –> repackaged into synaptic vesicles
Then diffusion into vascular system around neuron
Dopamine:
Synthesis:
Tyrosine hydroxylase pre-cursor –> Dopamine
Dopa Decarboxylase –> Dopamine
Effects on postsynaptic cell: EPSP
Acts on metabotropic receptors (G-protein coupled)
Removal:
- Re-uptake via DAT transporter
- Reuptake into presynaptic cell or surrounding glial cells via NET transporter
- Degraded by momoamine oxidase (MAO) or COMT inside cell –> repackaged into synaptic vesicles
Then diffusion into vascular system around neuron
Name 2 Amino acid neurotransmitters.
What is their general removal mechanism?
What is that?
How does that relate to action potentials?
Glutamate:
- Primary excitatory AA NT in CNS
- Found widely in CNS
- Synthesized from glutamine
- Major excitatory, binding to at least 4 receptors (metabotropic/ionotropic)
- Uptake by glia and the presynaptic terminal
- Reconverted to glutamine
- Returned to Neuron
Name 2 Amino acid neurotransmitters.
What is their general removal mechanism?
What is that?
How does that relate to action potentials?
GABA = hyperpolarization of post-synaptic cell
- Primary inhibitory NT of CNS- shuts things down
- Synthesized from glucose
- Converted to glutamate
- Widely distributed
- Removal is take up by glia OR degraded by enzymes
AP Relationship: Generates IPSPs in the post-synaptic cell
Fast chemical synaptic transmission:
- GABAa receptor is ionotropic (ligand-gated)
- Cl- channel, leading to a hyperpolarization of the post-synaptic cell
- Chlorine enters the cell
Slow chemical synaptic transmission:
- GABAb receptor, g-protein receptor linked to K+ channels (no second messenger involvement)
- Increases K+ conductance and hyper polarizes the post-synaptic cell
Where are neuropeptides synthesized?
Rough ER
Maturation of Neuropeptides
Occurs after packing into vesicles
T or F:
Multiple types of neuropeptides are released by a single vesicle
True
Can also be released by the same neuron with small molecule NT’s
Can act like hormones- released- drift into bloodstream- can effect a post-synaptic neuron far away
Initiate their effects by binding metabotropic receptors
Removal: broken down into AA’s by peptidases
Need relatively low concentrations to act on receptor
Small clear vesicles can be released by:
A. Relatively high levels of Ca2+
B. Relatively low levels of Ca2+
C. Inhibitory NT’s
D. Excitatory NT’s
Both:
A. Relatively high levels of Ca2+
B. Relatively low levels of Ca2+ (localizaed)
After a NT is released it:
A. Can be recycled by the glial cells
B. Can be removed by diffusion
C. Can be removed by enzymes
D. All of the above
E. A & C are correct
A. Can be recycled by the glial cells
B. Can be removed by diffusion
C. Can be removed by enzymes
T or F: Acetylcholine always acts rapidly
False- can act on ionotropic and metabotropic receptors
Acts rapidly in the muscle- ionotropic nicotinic receptors
Mature neuropeptides are made:
A. from precursors that are taken into the terminal
B. In the cell body
C. In the vesicles at the neuron terminal
D. In the axons of the neuron
C. In the vesicles at the neuron terminal
When an NT binds to a metabotropic receptor:
A. The receptor is found on an ion channel that immediately opens
B. The response of the receptor is relatively fast
C. The receptor activates 2nd messenger cascade to open an ion channel
D. It always causes an IPSP or inhibitory response
C. The receptor activates 2nd messenger cascade to open an ion channel
