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Biochemistry III > Cholinergic Neurotransmission > Flashcards

Cholinergic Neurotransmission Flashcards

1
Q

Where are cholinergic neurons located?

A
  • neuromuscular junction
  • autonomic preganglionic fibers
  • parasympathetic postganglionic fibers
    • heart, glands, smooth muscle
  • central nervous system
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2
Q

How is acetylcholine synthesized and where?

A

Acetyl CoA + Choline ⇔ CoA + Acetylcholine

catalyzed by choline acetyltransferase

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3
Q

Where is “low affinity” choline uptake and what is the KM ?

A

all tissues

KM > 10 μM

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4
Q

Where is “high affinity” choline uptake and what is the KM ?

A

only in cholinergic neurons

Na+ dependent

KM 1-5 μM

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5
Q

What is an inhibitor of “high affinity” choline uptake?

A

hemicholinium

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6
Q

Draw a schematic representation of how acetylcholine is taken into the vesicle.

A
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7
Q

What is the release of acetylcholine triggered by?

A

Ca2+

acion potential → depolarization of the axon terminal → Ca2+ entry via voltage-gated Ca2+ channels → exocytosis

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8
Q

Explain the process of exocytosis of the synaptic vesicles

A
  1. Uptake of neurotransmitter into vesicle
  2. Formation of cluster of vesicles- reserve pool
  3. Docking of vesicles in the active zone
  4. Priming- vesicles become competent for Ca2+ induced fusion
  5. Ca2+ signal- fusion (fusion pore- in the lipid bilayer
  6. Vesicle recycling
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9
Q

What are the different types of “recycling”

A
  • local recycling “kiss and stay”
  • fast recycling (reserve pool) no endosomal processing “kiss and run”
  • classical endocytosis
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10
Q

Are SNARE proteins and synaptotagmin involved in docking (stupid card)

A

NO

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11
Q

Explain the step of Priming in detail

A
  • formation of SNARE complex and association of synaptotagmin to the complex
  • vesicles and the plasma membrane are in close proximity

*unstable intermedier*

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12
Q

What does the Ca2+ signal induce?

A

the movement of synaptotagmin C2 domain into the phospholipid membrane

causes mechanical instability → fusion

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13
Q

Where are SNARE proteins located?

A

synaptic vesicles

plasma membrane

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14
Q

What are the SNARE proteins in the synaptic vesicles?

A

VAMP

(vesicle associated membrane protein)

Synaptobrevin

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15
Q

What are the SNARE proteins in the plasma membrane?

A

syntaxin 1A/B

SNAP-25

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16
Q

What provides the energy for the fusion of the vesicles and the plasma membrane?

A

SNARE motifs spontaneously form long

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17
Q

How many aminoacids do SNARE proteins contain?

A

70 aminoacid homolog sequence (SNARE MOTIF)

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18
Q

Describe the fusion-core complex.

A

paralell helices are formedwith the SNARE sequences that span into the cytosol (4 sequences from 3 proteins)

They are formed spontaneously in vitro between SNARE motifs

VAMP2- Syntaxin 1- SNAP 25

19
Q

Fusion of the v- SNARE and the t-SNARE schematic

20
Q

What do botulinum toxins do?

A

INHIBITORS of the cholinergic neurotransmission

in the cytosol LC (catalytic domain) it inhibits exocytosis

21
Q

Explain the components of botulinum toxins.

A

anaerob bacteria from clostridium botulinum

7 neuro-toxin

heavy chain (HC, 100kD) + light chain (LC, 50 kD)

22
Q

How are botulinum toxins taken up into the cholinergic terminals?

A

acceptor-mediated endocytosis

23
Q

What are botulinum toxins dependent on?

A

Zn2+ dependent endoproteases

absolute specificity for certain sites in the SNARE proteins

24
Q

What affects the stability of SNARE complexes?

A

can be increased or decreased by botulinum toxins

25
Where are **muscarinic receptors** located?
organs innervated by postganglionic parasympathetic neurons works via central nervous system
26
What is the molecular mechanism of a **muscarinic receptor**?
PLC activation [Ca] INHIBITION of adenylate cyclase activation of K+ channels
27
Where are **nicotinic receptors** located?
neuromuscular junction
28
What is the **molecular mechanism** of **nicotinic receptors**?
Na+, K+ channels
29
What effect do nictonic receptors have on striated muscle and the CNS?
ionotropic
30
What is a muscarinic receptor **antagonist?**
atropine
31
What is a **nicotinic** receptor **antagonist**?
curare
32
What are the effects of **nicotinic receptors** on **striated muscle**?
* Na+ and K+ permeability * membrane depolarization * Ca2+ release from SR
33
What is a **competitive inhibitor** of **nicotinic** receptors in **skeletal muscle**?
D tubocuranine
34
What is the effect of α-bungarotoxin?
Obtained from the venom of a snake ## Footnote **blocks muscular nicotinic receptors**
35
Events following the stimulation of nicotinic receptors in skeletal muscle
36
What is **malignant hyperthermia** and what are the effects of it?
mutation of the **r****yanodin receptor** * altered kinetics of Ca2+ channels * persistent long increase in [Ca2+]i \* can result in either\* a. ) hypermetabolism (fever) b. ) persistent activation of the contractile system (muscle rigidity)
37
What is the function of **acetylcholinesterase (serin protease)**
hydrolysis of acetylcholine | (located within the synapse)
38
What is acetylcholine esterase specific for?
acetylcholine
39
What is the function of **pseudocholinesterase**?
hydrolysisof other esters •short lasting muscle relaxants Example: suxamethonium
40
What is the importance of acetylcholineesterase?
* physiological * pharmacological → reversible inhibition * toxicological → irreversible inhibition
41
What are reversible cholinesterase inhibitors?
* diagnostic tests * Myasthenia gravis * short lasting drug is used * therapy of Myasthenia gravis * physostigmin, neostigmin → longer lasting drugs * eye drops * glaucoma
42
What is an example of an **irreversible cholinesterase inhibitor**?
organic phosphate molecules ## Footnote **diisopropyl-flurophosphate (DFP)**
43
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Biochemistry III (8 decks)

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