Brainscape's Knowledge GenomeTM

Browse over 1 million classes created by top students, professors, publishers, and experts.


See full index

Physiology I: Cellular Neuro > Lecture 11: Neuromuscular Junction > Flashcards

Lecture 11: Neuromuscular Junction Flashcards

1
Q

An action potential arrives at the nerve terminal and causes

A
  • Synaptic membrane to depolarize
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
2
Q

The depolarization of the synaptic membrane triggers

A
  • Voltage-gated calcium channels (N-type) to open there
  • Allows entry of calcium ions
  • Raises their concentration within
  • Leading to movement, fusion and release of the content of transmitter vesicles in the nerve terminal
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
3
Q

The transmitter, acetylcholine (ACh), takes

A
  • 10μs to diffuse across the 20 nm gap (synaptic cleft) from the pre-synaptic release site to the post-synaptic membrane on the myocyte (the end plate)
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
4
Q

ACh binds to and opens

A
  • Nicotinic ACh receptors (nAChR) on the tops of folds in the end plate membrane
  • AChRs form channels called ligand-gated channels (they are triggered by binding of ACh not by voltage change)
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
5
Q

The movement of ions depolarizes the end plate membrane, which is detected by

A
  • Additional voltage-gated Na+ channels in the bottoms of folds of the end plate membrane
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
6
Q

The Na+ channels open, thereby further increasing

A
  • The amount of depolarization of the post-synaptic membrane
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
7
Q

The current flowing at the end plate is sufficient to cause

A
  • The spread of the depolarization (called the end plate potential [EPP]) to the surrounding membrane outside the end-plate region
  • End plate membrane has a very high threshold to AP production and does not itself fire APs
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
8
Q

Activation of voltage-gated Na+ channels in the extra-junctional membrane, which has lower threshold to AP production, leads to

A
  • Triggering of an action potential that is propagated away from the NMJ and depolarizes the entire muscle fiber
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
9
Q

Muscle action potential production occurs at

A
  • The extra-junctional membrane
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
10
Q

Synthesis of ACh via Choline-o-acetyltransferase (ChAT)

A
  • Choline not synthesized by motor neuron while acetyl CoA is
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
11
Q

Destruction of ACh is achieved by

A
  • Acetylcholinesterase (AChase)
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
12
Q

Acetylcholinesterase (AChase)

A
  • Attached to basal lamina (fine connective tissue filling synaptic space)
  • Breaks ACh into acetate choline
  • Diffusion away (very little)
  • Some ACh is taken back up in about 30-40 msec (very little)
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
13
Q

Choline is actively reabsorbed within

A
  • 5-10 msec

- Na-dependant process

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
14
Q

Characteristics of end plate potentials (EPPs)

A
  • Graded potential (assive, non-regenerative, electrotonic, decremental)
  • Magnitude and duration normally large enough to evoke muscle action potential (AP)
  • Always excitatory
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
15
Q

Between _____ are released per action potential in nerve terminal

A
  • 100 - 300 vesicles (several quanta)
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
16
Q

Threshold is always reached with EPPs because

A
  • ACh released is 3+ times greater than that needed
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
17
Q

Nature of the ACh receptor

A
  • About 107 - 108 AChRs per end plate
  • Density 20,000/um2 (may be maximal of 50,000/um2)
  • Channel is closed until an ACh molecule attaches to binding site on each alpha (a) subunits
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
18
Q

Five subunits of ACh receptor

A
  • Two alphas
  • One each of beta, delta, epsilon
  • Together these create a non-specific cation channel
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
19
Q

Binding of ACh molecule to alpha site causes

A
  • A conformational change, resulting in the opening of channel
  • Positive ions flow through channel
  • Negative ions do not due to high density of negative charges at its mouth
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
20
Q

Denervation effects of ACh receptor

A
  • Spread of AChR over entire sarcolemma
21
Q

Denervation supersensitivity

A
  • Replacement of e subunit with g subunit leads to increased sensitivity to ACh
  • Channel opening time becomes 10X shorter
  • Only 1 ACh molecule is needed to open channel
22
Q

Examples of ACh mimetics

A
  • Methacholine
  • Carbachol
  • Nicotine
23
Q

ACh mimetics (Methacholine, Carbachol, Nicotine)

A
  • Not destroyed by cholinesterase
  • Dissipated slowly
  • Leads to prolonged EPPS
  • Can causing repeated APs and thus spasms
24
Q

All ACh mimetics prolong

A
  • Na channel opening times
25
Q

ACh inhibitors

A
  • Curare

- Alpha-bungarotoxin

26
Q

Curare

A
  • d-tubocurarine the most active ingredient
  • Binds competitively to the AChR
  • Effect lasts 30’ to 8 hrs, based on dosage
  • Ineffective if introduced orally
27
Q

Antidote to curare

A
  • AChEs
  • They prolong the half-life of ACh
  • Allow these molecules to compete out the curare
28
Q

Alpha-bungarotoxin (snake venom)

A
  • Neurotoxin that binds ACh receptor almost irreversibly

- Other snake alpha toxins also paralyze prey by binding to ACh receptor

29
Q

Anti-cholinesterses

A
  • Stigmine drugs
  • Edrophonium
  • Nerve gas (diisopropyl fluorophosphate)
30
Q

Stigmine drugs

A
  • Physostigmine
  • Neostigmine (a derivative)
  • Inhibit the cholinesterase and therefore prolong the action of ACh
31
Q

Edrophonium

A
  • Synthetic anti-cholinesterase acts similarly
32
Q

Nerve gas (diisopropyl fluorophosphate)

A
  • Inhibits AChE for weeks
33
Q

ACh release inhibitors

A
  • Botulinus toxin
  • Tetanus toxin
  • Pb and Cd
34
Q

Botulinus toxin

A
  • From C. botulinum
  • Reduces amount of AChreleased by disrupting SNARE docking proteins involved in neurotransmitter release
  • Leads to flaccid paralysis
35
Q

Tetanus toxin

A
  • From C. tetani
  • Enters a NMJ and travels retrogradely along a-motor neurons to spinal cord and enters presynaptic boutons of inhibitory neurons to disrupt SNARE docking proteins involved in neurotransmitter release
  • Leads to spastic paralysis, e.g. risus sardonicus of facial muscles
36
Q

Pb and Cd

A
  • Inhibit transmitter release by diminishing Ca entry in presynaptic terminal
37
Q

Reuptake inhibitors

A
  • Hemicholinium
38
Q

Hemicholinium

A
  • Blocks choline reuptake into terminal

- Reduces amount in quanta (later stages)

39
Q

Myasthenia Gravis

A
  • Autoimmune

- Progressive disease

40
Q

Transmission: sequence of events

A
  • Depolarization of axon terminal membrane
  • Opening of Cav channels in terminal membrane
  • Entry of Ca into axon terminal
  • Fusion of synaptic vesicles with membrane
  • Release of ACh into synaptic cleft
  • Diffusion of ACh across synaptic cleft
  • Binding of ACh to AChR in postsynaptic membrane
  • Generation of postsynaptic potential
41
Q

Calcium entry into the axon terminal is

A
  • An absolute requirement
42
Q

Neurotransmitter is released in discrete amounts ot

A
  • Quanta (packets)

- Size of the quanta may vary from system to system

43
Q

All spontaneous post-synaptic potentials are _____ of these quanta

A
  • Integer multiples
  • i.e. 2x, 3x or 4x as large
  • ever fractionally larger, i.e. 1.5x, 2.6682x
44
Q

ACh receptor protein

A
  • Pentameric protein

- Muscle variety permeable to all cations but only Na+ ions pass

45
Q

Mimetics effects on EPPs

A
  • Prolong synaptic activity
  • Nicotine, succinylcholine, methacholine
  • Longer lasting EPPs
  • Greater probability of EPPs reaching extra-junctional membrane and firing of action potentials
46
Q

Inhibitors effects on EPPs

A
  • Reduce/abolish activity
  • Curariform drugs (tubocurarine)
  • Used in surgery to cause flaccid paralysis
47
Q

Enhancers effects on EPPs

A
  • Anti-cholinesterases
  • Drugs that inhibit the breakdown of ACh
  • Stigmine-derived drugs (eserine)
48
Q

Pathologies of EPP

A
  • ACh release inhibitors (botulinus, tetanus, Pb2+)
  • Myasthenia gravis
  • Channelopathies
49
Q

EPP Channelopathies

A
  • Lambert-Eaton syndrome (Cav antibodies)

- Slow channel syndrome (prolonged AChR opening)

Physiology I: Cellular Neuro (8 decks)

Brainscape helps you reach your goals faster, through stronger study habits.
© 2024 Bold Learning Solutions. Terms and Conditions