neurotransmitters 2
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- what are the two types of synapses and how do they differ?
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electrical synapse allows direct, passive electrical current to pass through gap junction from one neuron to another
chemical synapse releases neurotransmitter from one neuron across synaptic cleft to another neuron, where binding to receptors causes opening or closing of ion channels and subsequently an electrical signal that acts on post-synaptic neuron and is either inhibitory or excitatory - how does calcium enter the pre-synaptic neuron and what does it do?
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action potential depolarizes the cell, allowing voltage-gated calcium channels to open
calcium enters through open channels and stimulates fusion of synaptic vesicles with the pre-synaptic plasma membrane for neurotransmitter release - describe the transmission that occurs between electrical synapses
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transmission of large molecules by direct passive electrical current through gap juction that links two neurons
paired channels form a pore
ATP, 2nd messengers
transmission is bidirectional and very fast - describe the cycle of transmission between electrical synapses
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action potential generates electrical current, which flows directly from one neuron to another through pore in that comprises gap junction
transmission is bidirectional and very fast - what is the function of electrical synapses? give examples
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synchronize electrical activity among populations of neurons
brainstem neurons - breathing
hormone-secreting neurons: all cells fire action potential at the same time to release a burst of hormone into the circulation - mammary glands
coordinated intercellular signaling and metabolism (glial cells form large interconnected networks) - describe the cycle that occurs at chemical synapses (10 steps)
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1. neurotransmitter synthesized and stored in synaptic vesicles at nerve terminal
2. action potential invades nerve terminal, depolarizing pre-synaptic neuron
3. depolarization opens voltage-gated calcium channels, allowing calcium influx into cell
4. increased calcium concentration stimulates fusion of synaptic vesicles with plasma membrane of pre-synaptic neuron
5. neurotransmitter released into synaptic cleft via exocytosis
6. neurotransmitter binds to receptors on post-synaptic neuron membrane
7. post-synaptic ion channels open or close
8. ions flow into or out of open/closed ion channels, creating an electrical current through the post-synaptic cell
9. this current causes a change in post-synaptic potential, which changes the excitability of the post-synaptic cell
10. vesicle membrane is retrieved from plasma membrane of pre-synaptic cell. it is recycled to make a new synaptic vesicle - name 3 places where acetylcholine acts
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released by vagus nerve to regulate heartbeat
neuromuscular junctions of striated muscles
visceral motor system -
what are the 2 types of neurotransmitters and how do they differ?
distinguish between how they are released and what type of synaptic actions they mediate -
small molecule neurotransmitters (subset of this group is the biogenic amines) and peptide neurotransmitters
small molecule transmitters are released by low frequency activity and mediate rapid synaptic actions
peptide transmitters are releasted by high frequency activity and mediate slower, ongoing synaptic actions - what is a co-transmitter and what is its significance?
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neurons often store and release 2 or more neurotransmitters (co-transmitters)
a neuron can be excited by 1 type of neurotransmitter and inhibited by another type - name the 3 criteria that define a neurotransmitter
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1. substance must be present within pre-synaptic neuron
2. substance must be released in response to depolarization of the pre-synaptic cell membrane and release must be Ca-dependent
3. specific receptors for the substance must be present on the post-synaptic cell membrane -
describe the differences in synthesis, storage, and transport between small molecule neurotransmitters and peptide neurotransmitters
location of synthesis
transport
vesicles -
enzymes needed to synthesize small molecule neurotransmitters are produced in the neuronal cell body and transported to the nerve terminal by slow axonal transport
precursor molecules are taken into the cell by transporter proteins
small molecule neuropeptides are synthesized at the nerve terminal and stored in small clear-core synaptic vesicles
neuropeptides are synthesized in the cell body of the neuron and transported to the nerve terminal by fast axonal transport
neuropeptides are transported and stored in large dense-core vesicles - name 4 components of neurotransmitter removal from synaptic cleft
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1. diffusion away from post-synaptic receptors
2. re-uptake into pre-synaptic nerve terminal by transporter proteins
3. uptake into nearby glial cells
4. degradation by specific enzymes -
what are the two types of neurotransmitter receptors and how do they differ?
distinguish between both speed and duration of post-synaptic response -
ionotropic receptor = ligand-gated ion channel = molecule that is both receptor and ion channel allows fast post-synaptic response that lasts only a short time
metabotropic receptor = molecule that is a receptor only, not an ion channel allows slower post-synaptic response that persists for a longer time - give 4 examples of small molecule neurotransmitters
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Ach
GABA
glycine
glutamate - name the 5 biogenic amines
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the catecholamines: dopamine; epi; norepi
serotonin
histamine - name the 2 precursors and the enzyme used to synthesize Ach
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Acetyl CoA (from glucose metabolism) and choline
enzyme is CAT = choline acetyltransferase - where does the choline for Ach synthesis come from?
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choline is present in the plasma at high concentrations
it is taken up into the pre-synaptic neuron by a Na-dependent choline transporter -
what are the breakdown produces of Ach and what enzyme produces them?
what happens to the breakdown products? -
acetylcholinesterase breaks Ach down into acetate + choline
choline is transported back into the nerve terminal - what happens if acetylcholinesterase is inhibited?
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Ach accumulates at the synapse, depolarizing the post-synaptic neuron
the post-synaptic neuron is thus refractory to subsequent Ach release: can't open ion channels in the cell
result is neuromuscular paralysis - what are the inhibitors of acetylcholinesterase?
- organophosphates, e.g. Sarin
- describe the structure and function of a nicotinic Ach receptor
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activated by both nicotine and Ach
same molecule is both receptor and cation channel (ionotropic receptor / ligand-gated ion channel)
large protein complex with 5 subunits around a central membrane-spanning pore
each subunit has 4 transmembrane domains that comprise the ion channel pore and a long extracellular region where the Ach binds
intimate association of Ach with channel pore allows rapid (ionic) response to Ach
results in excitatory post-synaptic responses - alpha-bungarotoxin
- binds to nicotinic Ach receptors at neuromuscular junctions but not at neuronal junctions
- describe the function of a muscarinic Ach receptor
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activated by both muscarine and Ach
just a receptor, not an ion channel (metabotropic)
mediates most of the effects of Ach in the brain - name 3 places where muscarinic Ach receptors are important
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1. forebrain
2. ganglia of PNS
3. autonomic effector organs: heart; smooth muscle; exocrine glands - give 3 examples of blockers of muscarinic Ach receptors that have therapeutic value
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1. atropine - pupil dilation
2. scopolamine - prevent motion sickness
3. ipratropium - treats asthma - atropine
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pupil dilation
blocker of muscarinic Ach receptor - scopolamine
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prevents motion sickness
blocker of muscarinic Ach receptor - ipratropium
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asthma treatment
blocker of muscarinic Ach receptor - how does cocaine work?
- it binds to DAT (dopamine transporter that transports dopamine out of synaptic cleft), increasing the dopamine concentration so dopamine is more available to receptors
- conotoxin peptides
- toxins that block nicotinic Ach receptors
- what is the function and significance of biogenic amines?
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regulate many brain functions
defects lead to psych disorders
psych drugs and drugs of abuse act on pathways, synthesis, receptor binding, and catabolism of biogenic amines - tyrosine hydroxylase
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converts tyrosine to DOPA in first and rate-limiting step of catecholamine synthesis
requires oxygen and tetrahydrobiopterin as co-factors - DOPA decarboxylase
- coverts DOPA to dopamine
- dopamine-beta-hydroxylase
- converts dopamine to norepi
- phenylethanol-amine-N-methyl transferase
- converts norepi to epi
- pathway of catecholamine synthesis
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tyrosine to DOPA to dopamine to norepi to epi
tyrosine hydroxylase catalyzes rate-limiting step - dopamine
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motivation, reward, reinforcement - dopamine transporter blocked by cocaine so more dopamine available to receptors
present in coprus striatum, which coordinates body movements
in Parkinson's disease, substantia nigrans degenerates so no more input to corpus striatum so motor dysfunction - VMAT
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vesicular monoamine transporter
loads dopamine into synaptic vesicles at the nerve terminal - DAT
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Na-dependent dopamine transporter
transports dopamine from the synaptic cleft into nerve terminals and glial cells
inhibited by cocaine - MAO
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dopamine catabolism enzyme contained in both neurons and glia
monoamine oxidase
inhibited by antidepressants - COMT
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dopamine catabolism enzyme contained in both neurons and glia
catechol-O-methyl transferase
inhibited by antidepressants - how does dopamine work?
- it activates G-protein-coupled receptors
- Ach post-synaptic effect
- excitatory
- Ach precursors
- acetyl CoA + choline
- Ach synthesis rate-limiting step
- CAT (choline acetyl transferase)
- Ach removal
- degraded by acetylcholinesterase
- Ach storage vesicle
- small clear-core vesicle
- glutamate post-synaptic effect
- excitatory
- glutamate precursors
- glutamine
- glutamate synthesis rate-limiting step
- glutaminase
- Ach properties
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excitatory post-synaptic effect
rate-limiting step is CAT (choline acetyl transferase)
precursors are choline + acetyl CoA
removal is by acetylcholinesterase
storage vesicles are small clear-core vesicles - glutamate properties
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excitatory post-synaptic effect
glutamine is precursor
rate-limiting step in synthesis is glutaminase
removal is by transporters
storage vesicles are small clear-core vesicles - glutamate removal
- transporters
- glutamate storage vesicles
- small clear-core vesicles
- GABA post-synaptic effect
- inhibitory
- GABA precurors
- glutamine
- GABA synthesis rate-limiting step
- GAD
- GABA removal
- transporters
- GABA storage vesicles
- small clear-core vesicles
- GABA properties
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inhibitory post-synaptic effect
precursor is glutamine
rate-limiting step in synthesis is GAD
removal is by transporters
vesicles are small clear-core vesicles - glycine post-synaptic effect
- inhibitory
- glycine precurors
- serine
- glycine synthesis rate-limiting step
- phosphoserine
- glycine removal
- transporters
- glycine vesicles
- small clear-core vesicles
- glycine properties
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inhibitory post-synaptic effect
precursor is serine
rate-limiting step in synthesis is phosphoserine
removal is by transporters
vesicle is small clear-core vesicle - catecholamine post-synaptic effect
- excitatory
- catecholamine precursor
- tyrosine
- catecholamine synthesis rate-limiting step
- tyrosine hydroxylase
- catecholamine removal
- transporters; MAO; COMT
- catecholamine vesicles
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small dense-core vesicles
large irregular dense-core vesicles - catecholamine properties
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excitatory post-synaptic effect
precursor is tyrosine
rate-limiting step in synthesis is tyrosine hydroxylase
removal is by transporters, MAO, and COMT
vesicles are small clear-core vesicles and large irregular dense-core vesicles - serotonin post-synaptic effect
- excitatory
- serotonin precursor
- tryptophan
- serotonin synthesis rate-limiting step
- tryptophan hydroxylase
- serotonin removal
- transporters, MAO
- serotonin vesicles
- large dense-core vesicles
- serotonin properties
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post-synaptic effect is excitatory
precursor is trp and rate-limiting step in synthesis is trp hydroxylase
removal is by transporters and MAO
vesicles are large dense-core vesicles - histamine post-synaptic effect
- excitatory
- histamine precursor
- histidine
- histamine synthesis rate-limiting step
- histidine decarboxylase
- histamine removal
- transporters
- histamine vesicles
- large dense-core vesicles
- histamine properties
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excitatory post-synaptic effect
precuror is histidine and rate-limiting step is histidine decarboxylase
removal is by transporters
vesices are large dense-core vesicles - ATP post-synaptic effect
- excitatory
- ATP precursor
- ADP
- ATP synthesis rate-limiting step
- mitochondrial ox-phos and glycolysis
- ATP removal
- hydrolysis to AMP and adenosine
- ATP vesicles
- small clear-core vesicles
- ATP properties
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excitatory post-synaptic effect
precursor is ADP
rate-limiting steps are glycolysis and mitochondrial ox-phos
removal is by hydrolysis to adenosine and AMP
vesicles are small clear-core vesicles - neuropeptides post-synaptic effect
- excitatory and inhibitory
- neuropeptides precursors
- amino acids
- neuropeptides synthesis rate-limiting step
- synthesis in neuronal cell body and fast axonal transport (ATP-dependent) in large dense-core vesicles to nerve terminal
- neuropeptides removal
- proteases
- neuropeptides vesicles
- large dense-core vesicles
- neuropeptides properties
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post-synaptic effects are excitatory and inhibitory
precursors are amino acids
rate-limiting steps are synthesis in neuronal cell body and ATP-dependent fast axonal transport to nerve terminal
removal is by proteases
vesicles are large dense-core vesicles - which neurotransmitters have inhibitory post-synaptic effects?
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GABA and glycine
sometimes neuropeptides
all others have excitatory post-synaptic effects - Parkinson's disease
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dopaminergic neurons of substantia nigra degenerate
substantia nigra input to corpus striatum is compromised, resulting in motor dysfunction