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Physiology > Neurotransmission > Flashcards

Neurotransmission Flashcards

1
Q

Describe chemical transmission

A

Chemical transmission: neurotransmitters in vesicles
- Small clear vesicle –> glutamate,
GABA, acetylcholine, glycine - - Small vesicle with dense core –>
catecholamine’s
- Large vesicle with dense core –>
neuropeptides

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2
Q

Describe electrical transmission

A

Electrical transmission: electrical gradient based on ion movements
- Need to reach threshold for propagation of action potential
- Lowest threshold is @ the initial segment, just caudal to the axon hillock

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3
Q

Describe excitatory post synaptic potential (EPSP).

A

Excitatory post synaptic potential (EPSP)
- Depolarization response
- Opening of Na+ or Ca2+ channels in post synaptic neuron (influx)
- Summation of depolarization eventually reach threshold potential
- Action potential will then be propagated
- Slow EPSP = ↓ conductance of K+

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4
Q

Describe Inhibitory post synaptic potential (IPSP).

A

Inhibitory post synaptic potential (IPSP)
- Hyperpolarization response
- Opening of Cl- channels in post synaptic neuron (influx) –> membrane potential now more (-)
- Slow IPSP = ↑ conductance of K+

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5
Q

What’s the difference between direct and indirect inhibition?

A

Direct inhibition - ex. Post synaptic inhibition of IPSP
- Not a direct consequence of a previous
post synaptic neuron

Indirect inhibition
- Due to effect of previous post synaptic
neuron discharge
○ Ex. Refractory period
○ Hyperpolarization
Ex. Repeated firing in spinal cord

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6
Q

What’s the difference between pre- and post- synaptic inhibition?

A

Pre synaptic inhibition
- Neuron acts on another excitatory neuron to ↓ excitatory neurotransmitter release (axoaxonal synapse_

Post synaptic inhibition
- Inhibitory neurotransmitters from an inhibitory neuron acts directly on the post synaptic neuron

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7
Q

Describe how action potential is generated at the neuromuscular junction.

A

Neuromuscular junction
- Axon of motor neuron ends @ motor end plate of muscle
- Action potential carried by the motor nerve
- Ca2+ influx
- Exocytosis of acetylcholine in synaptic vesicles
- Acetylcholine binds to receptors on the motor end plate
- Na+ influx, K+ efflux –> depolarization
- Action potential generated –> propagated in both direction along the sarcolemma
- Muscle contraction occurs

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8
Q

Describe how glutamate, gaba, acetylcholine, seretonin, and catecholamines are made. ***

A
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9
Q

Describe the action of glutamate as a neurotransmitter

A

Glutamate = main excitatory transmitter in CNS
- Produced in Krebs’ cycle via GABA transaminase, or
- In glial via glutamine synthetase
3 main receptors:
1. AMPA
2. Kainate
3. NMDA
NMDA - opens when glutamate binds to it
Needs less Mg (depolarization) by activation of AMPA and kainite receptors
NMDA receptor agonist can be used to treat chronic pain

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10
Q

How is glutamate secreted?

A

Glutamate Secretion
- Produced in mitochondria via Kerbs’ cycle from glutamine
- Concentrated into vesicles by vesicular glutamate transporter
- Exocytosis out –> G-coupled or ionotropic receptors on post synaptic membrane
- Reuptake facilitated by Na+ dependent glutamate transporters
- Can go into glia cell, converted to glutamine via glutamine synthetase, diffuse back to nerve, and hydrolyzed back to glutamate

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10
Q

How is glutamate secreted?

A

Glutamate Secretion
- Produced in mitochondria via Kerbs’ cycle from glutamine
- Concentrated into vesicles by vesicular glutamate transporter
- Exocytosis out –> G-coupled or ionotropic receptors on post synaptic membrane
- Reuptake facilitated by Na+ dependent glutamate transporters
- Can go into glia cell, converted to glutamine via glutamine synthetase, diffuse back to nerve, and hydrolyzed back to glutamate

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11
Q

What’s the function and main receptors for GABA?

A

GABA = main inhibitory neurotransmitter
- Formed by decarboxylation of glutamate via glutamate decarboxylase (GAD)
- Transported into vesicles by vesicular GABA transporter (VGAT) –> does both GABA and glycine

Receptors:
- GABA a & GABA b = widely distributed in CNS
- GABA c = almost exclusively in retina of adult vertebrates
- GABA a & GABA c = ionotropic receptors –> Cl- entry
- GABA b = G coupled-protein receptor –> influences Na+/Ca2+ influx
- GABA a –> beznodiazapam ↑Cl-conductance
○ Barbiturates will enhance it’s inhibitory effect , also suppress AMPA receptor-mediated excitation
○ Low level of activation all the time - to cut down noise from the other ones

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12
Q

What’s the action of glycine as a nuerotransmitter?

A

Glycine = both inhibitory and excitatory
- ↑sensitivity to glutamate if bound to NMDA receptor
- Also ↑Cl- conductance
- Cl- channel = glycine receptor for inhibitory effects

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13
Q

Described norepinephrine secretion.

A

Monoamine Secretion (norepinephrine)
- Production in the cytoplasm & secretory granules
- Concentration maintained by VMAT (vesicular monoamine transporter)
- Released into the synaptic cleft via exocytosis
- Many receptors on the postsynaptic membrane (G-protein coupled receptors)
- NET = norepinephrine transporter –> involved with reuptake
Generally not a mediator @ post synaptic endings

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14
Q

Described acetylcholine secretion.

A
  • Acetylcholine transported into vesicle via vesicle-associated transporter (VAT) –> peptide P and ATP also comes in
  • Exocytosis of vesicle requires opening of voltage-sensitive Ca2+ channels
    ○ Requires synaptosome-associated membrane proteins (SNAPs) and vesicle-associated membrane proteins (VAMPs)
  • Acetylcholine is metabolized by acetylcholinesterase on the post synaptic membrane
  • Modulation of acetylcholine release done via hetero receptors and acetylcholine autorecepto
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15
Q

What are the receptors for acetyhlcholine?

A

Muscarinic cholinergic
- Stimulating actions on smooth
muscles
- Coupled G-protein receptors

Nicotinic cholinergic
- Simulating actions on skeletal muscles and sympathetic ganglia
- Ion-gated –> allows Na+ entry when activated
- Neural ones also has high permeability for Ca2+

16
Q

Where are acetylcholine found?

A
  • Neuromuscular junction, autonomic ganglia, postganglionic parasympathetic nerve target organ junction, some postganglionic sympathetic nerve-target junctions
  • Secreted by all nerves that exit the CNS
  • Made in nerve terminal from choline and acetyl-CoA by choline acetyltransferase (ChaT)
  • Choline transported from extracellular fluids via choline transporter (CHT) –> needs Na+
17
Q

What are the dopamine receptors?

A

Dopamine
- Active reuptake post secretion into synaptic cleft via Na+ and Cl- dependent dopamine transporter
- Metabolized to inactive compound by MAO and COMT

Receptors
- D1 like (D1 and D2) or D2 like (D2, D3, and D4)
- All are metabotropic G-protein couple receptors
- Activation of D1 like ↑ cAMP; opposite for D2 like

18
Q

Describe serotonin

A
  • Aka 5-HT
  • Made from tryptophan
  • Tryptophan –> tryptophan hydroxylase –> 5-hydroxytryptophan –> aormatic L-amino acid decarboxylase –> 5HT
  • Transported into vesicle via VMAT
    It’s in chemoreceptor trigger zone! Used to treat nausea (ondansetron)
19
Q

What are the serotonin receptors? ***

A
  • 7 classes of 5-HT receptors; only 5-HT3 is not G-protein coupled receptor
  • 5-HT2a: mediates platelet aggregation and smooth muscle contraction
  • 5-HT2c: KO mice don’t respond to leptin (eat lots) and have fatal seizures
  • 5-HT3: GI, area postrema –> associated with vomiting
  • 5-HT4 : also in GI –> peristalsis, facilitate secretion. Also in brain
  • 5-HT6 & 5-HT7: also in brain –> 5-HT6 have high infinity for anti-depressants
20
Q

How is serotonin secreted?

A
  • Exocytosis after activation of voltage gated Ca2+ channel
  • Transported back via 5-HT transporter (serotonin transporter, SERT)
  • Auto receptor 5HT1D modulates 5-HT release
  • Reuptake ones are either sequestered in vesicle, or converted to 5-hydroxyindole acetaldehyde by mitochondrial monoamine oxidase
21
Q

What are enkephalins?

A

They are opioid peptides
- receptors that bind morphine are found in the brain and GI
- Enkephalins = endogenous ligand –> metenkephalin and leu-enkephalin
- They bind to opioid receptors, so are called opioid peptides
- Enkephalins
○ Nerve endings in GI tract and
many parts of brain
- Synaptic transmitter
- Also ↓ GI motility

22
Q

What are the 3 classes of opioid receptors?

A
  • µ, ĸ, δ
  • All are G-protein coupled receptors
  • Inhibit adenylyl cyclase
  • µ: ↑K+ conductance –> hyperpolarization
  • ĸ & δ: closes Ca2+ channels
23
Q

What is substance P?

A
  • Polypeptide with 11aa residue
  • Found in intestine, peripheral nerves, many parts of CNS
  • Other members of the family (Tachykinin) include neurokinin A and neurokinin B
  • Found in high concentration of primary afferent neurons in the spinal cord
    • 1st connection in the pain pathway
      • Involved in peristalsis in GI
24
Q

What are the 3 receptors for substance P?

A
  1. NK1-3
  2. All are metabotropic G-protein coupled receptors
  3. NK1 likes substance P (in CNS) –> IP3 and DAG
    - Receptor antagonist (maropitant) can be used for nausea
25
Q

What is nitric oxide (NO)?

A
  • Release by endothelium, and brain as well
  • Activates guanylyl cyclase (gas!) diffuses through membrane
  • Not stored in vesicles –> produced on demand
  • Synthesis can be activated by NMDA –> Ca2+ influx, activation of neuronal nitric oxide synthase
  • Could enhance release of glutamate
26
Q

What are the actions of endogenous cannabinoids?

A
  • 2-arachidonyl glycerol
  • Anandamide
  • Also not stored in vesicles
  • Synthesized in response to Ca2+
  • Act on CB1 receptor
    ○ G-protein mediated ↓extracellular
    cAMP
    ○ Common in central pain pathway
    ○ Agonists have anti-nociceptive
    effect
  • Retrograde synaptic messengers
  • CB2 receptors may be targeted for chronic pain therapy (doesn’t induce euphoria like CB1)
27
Q

How are catecholamine forms?

A
  • Norepinephrine, epinephrine, dopamine
  • Formed via tyrosine, which can be formed from phenlalanine - though they are mostly dietary origin
  • Tyrosine is transported in via Na+ dependent channel
  • Tyrosine –> Tyrosine hydroxtlase (TH) –> dopa –> dopa decarboxylase –> dopamine
  • Transported into vesicle via VMAT
  • Once inside vesicle, dopamine is converted to norepinephrine by dopamine β-hydroxylase
    ○ Only small molecule transmitter
    that’s produced in vesicle rather
    than transported in!
  • Can measure concentration in urine –> ex. For pheochromocytoma, not the best test, but can be done
28
Q

Which receptors do the catecholamines act on?

A
  • Epinephrine and norepinephrine both act on α & β adrenoceptors
    ○ Norep likes α, epi likes β
    ○ Metabotropic G-protein coupled
    receptors
29
Q

What’s the function of α-1 adrenergic receptors?***

A

Most α-1 adrenergic receptors lead to activation of IP3 and DAG –> ↑ intracellular Ca2+ release and activate protein kinase C
○ Excitatory
○ Smooth muscle and heart

30
Q

What’s the function of α-2 adrenergic receptors?***

A
  • Most α-2 adrenergic receptors activate G I inhibitory proteins to inhibit adenylyl cyclase and ↓cAMP
  • Other α-2 adrenergic receptors also lead to K+ influx –> hyperpolarization, and inhibit neuronal Ca2+ channels
    ○ Inhibitory
    ○ CNS, pancreatic islets cells, nerve
    terminals
31
Q

What are the functions of β-adrenergic receptors?***

A
  • β-adrenergic receptors activate stimulatory Gs protein to activate adenylyl cyclase to ↑cAMP
    ○ β-1 @ heart and renal
    juxtaglomerular cells
    ○ β-2 @ bornchial smooth muscle
    and skeletal muscle
    ○ β-3 @ adipose tissue
32
Q

What are the function of the histamine receptors?

A
  • H1, H2, H3
  • H3
    ○ Pre-synaptic, mediate inhibition of
    the release of histamine and
    others via G-protein
  • H1
    ○ Activate phospholipase C
  • H2
    ○ ↑intracellular cAMP
  • H4
    May regulate the immune system

Physiology (28 decks)

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