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MSK Exam II > Synaptic Transmission and Physiology Of NMJ > Flashcards

Synaptic Transmission and Physiology Of NMJ Flashcards

1
Q

Lowering the resting membrane potential below the equilibium potential for potassium will result in which of the following to occur?

A. More potassium will exit the cell
B. Less potassium will exit the cell
C. There will be no change on potassium
D. More sodium will enter the cell

A

B. Less potassium will exit the cell

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2
Q

Decreasing the extracellula potassium concentation will result in which of the following changes to resting membrane potential?

A. Become more negative
B. Become more positive
C. No change
D. Make it easier to depolarize

A

A. Become more negative

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3
Q

Which of the following would be an appropriate means to slow an action potential?

A. Reduce sodium permeability during phase 4
B. Increase sodium permeability during phase 0
C. Decrease sodium permeability during phase 0
D. Increase potassium permeability during phase 3

A

C. Decrease sodium permeability during phase 0

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4
Q

Compare the speed of electrical synapses vs. chemical synapses

A

Electrical synapses = FAST

Chemical synapses = Slower

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5
Q

What type of synapses are connected via gap junctions and allow multidirectional communication?

A

Electrical synapses

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6
Q

Cells that have shared cytosol that travels through pores known as ______ _______, made up of connexin molecules allowing multidirectional communication

A

Gap junctions

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7
Q

Which has a larger synaptic gap - electrical synapses or chemical synapses?

A

Chemical synapses

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8
Q

Describe directionality of communication at chemical synapses

A

Unidirectional

However - post-synaptic cell may secrete substances that feedback onto pre-synaptic cell

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9
Q

What are the 2 required steps at a chemical synapse?

A

Release of chemical from presynaptic cell

Reaction of chemicals by postsynaptic cell

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10
Q

The general sequence of events at a chemical synapse:

  1. Neuron synthesizes chemical ___________
  2. Neuron stores these in axon _________, or transports them to terminus
  3. An ________ ________ triggers the release of NTs into the synaptic cleft. Often ________ enters the cell.
A

Neurotransmitters

Terminals

Action potential; calcium

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11
Q

The general sequence of events at a chemical synapse:

  1. Neuron synthesizes chemical neurotransmitters
  2. Neuron stores neurotransmitters in axon terminals or transports them to terminus
  3. An action potential triggers the release of NTs into synaptic cleft; often calcium enters the cell
  4. Neurotransmitter diffuses across cleft and binds to _______ _______ receptor
  5. Post-synaptic response –> change in _______ _______
  6. NTs are taken back up into pre-synaptic terminus, diffuse away, or are enzymatically inactivated. There may also be some ______ from post-synaptic cell to pre-synaptic cell.
A

Post-synaptic

Membrane potential

Feedback

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12
Q

Describe the speed of the post-synaptic response at a chemical synapse

A

Can be fast or slow, and can result in the generation of an action potential

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13
Q

What type of response is elicited at a chemical synapse if K+ flows out and Na+ flows in, but not enough to induce an action potential? What is the result?

A

Excitatory post-synaptic potential (EPSP)

Result: membrane potential closer to threshold (hypopolarization)

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14
Q

T/F: with enough EPSPs, an action potential may be generated

A

True - this is the concept of summation

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15
Q

What type of response is elicited at a chemical synapse if K+ flows out of the cell or there is flow of negative charge into the cell?

A

Hyperpolarization

Result: membrane potential further away from threshold

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16
Q

_________ summation occurs at the same pre-synaptic neuron with a simple repeated signal

A

Temporal

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17
Q

________ summation occur due to different pre-synaptic neurons signaling together

A

Spatial

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18
Q

The calcium concentration is _________ outside the cell than inside

Calcium is thought of as a _________ messenger

A

Higher

Second

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19
Q

When it comes to changes at chemical synapses, the greater the increase in calcium in the cytosol, the greater the _____________ release

A

Neurotransmitter

[calcium is being released out of the cell constantly]

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20
Q

What are the 4 criteria of neurotransmitters?

A
  1. Must be synthesized and stored in an axon terminal
  2. Must be transported to pre-synaptic membrane and released in response to action potential
  3. Must interact with post-synaptic membrane receptors and elicit a response
  4. Must be inactivated
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21
Q

The first criteria of neurotransmitters is that it must be synthesized and stored in an axon terminal. What are the 2 conditions under which neurotransmitters may be developed?

A

Derived from food substrates - glutamate, glycine, and aspartate

Some are synthesized in the soma ofneurons then transported to axon terminal and encapsulated in synaptic vesicles

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22
Q

The second criteria of a neurotransmitter is that it must be released in response to an action potential.

This is dependent on which critical ion?

What is the unit of measurement for amount of neurotransmitter released?

A

Calcium

NTs are released as “quantals”

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23
Q

What is a simple equation for neurotransmitter release in terms of calcium release and action potential?

A

[increase in calcium] + [increase in action potential] = NT release

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24
Q

The 3rd criteria of a neurotransmitter is that the postsynaptic receptors receive a signal and respond.

How might you determine whether or not there has been a response at a post-synaptic receptor?

A

Exogenous application

Application of agonists and antagonists

High resolution histology (with radioactively labeled receptor Abs)

25
Q

The 4th criteria of a neurotransmitter is that it can be inactivated. How does this criteria relate to neurotransmitters as drug targets?

A

You can develop drugs that:

Increase the number of APs

Release NT from vesicles with or without impulse

Block reuptake or block post-synaptic receptors (SSRIs)

Produce more or less NT

Prevent vesicles from releasing NT

Prolong or increase clearance or inactivation

26
Q

What are some examples of the following classes of NTs:

Choline esters

Biogenic amines

A

Choline esters = acetylcholine (ACh)

Biogenic amines = dopamine, epinephrine, norepinephrine, serotonin

27
Q

What are some examples of the following classes of NTs:

Amino acids

Neuropeptides

A

Amino acids: glutamate, glycine, GABA

Neuropeptides: ACTH, glucagon, endorphins

28
Q

________ is an NT used by the spinal cord neurons to control muscles and by many neurons in the brain to regulate memory. In most instances it is EXCITATORY

A

Acetylcholine

29
Q

__________ is an NT that produces feelings of pleasure when released by the brain reward system. It has multiple functions depending on where it acts in the brain. It is usually INHIBITORY

A

Dopamine

30
Q

________ is the major inhibitory NT in the brain

A

GABA (gamma-aminobutyric acid)

31
Q

_________ is the most common excitatory NT in the brain

A

Glutamate

32
Q

________ is an NT used mainly by neurons in the spinal cord. It probably always acts as an inhibitory NT

A

Glycine

33
Q

_________ acts as an NT and a hormone. In the peripheral nervous system, it is part of the fight or flight response. In the brain, it acts as an NT to regulate normal brain processes. It is usually excitatory but it can be inhibitory in some brain areas

A

Norepinephrine

34
Q

_________ is an NT involved in many functions including mood, appetite, and sensory perception. In the spinal cord, it is inhibitory in pain pathways

A

Serotonin

35
Q

What are the 2 types of acetylcholine receptors? Which one is faster?

A

Nicotinic (ionotropic) = faster

Muscarinic (metabotropic)

36
Q

What is another term for nicotinic ACh receptors?

A

Ionotropic

37
Q

What is another term for muscarinic ACh receptors?

A

Metabotropic

38
Q

What type of ACh receptor, nicotinic or muscarinic, is responsible for muscle contraction?

A

Nicotinic (ionotropic)

39
Q

What type of ACh receptor, nicotinic or muscarinic, is responsible for parasympathetic responses?

A

Muscarinic (metabotropic)

40
Q

Nicotinic ACh receptors operate on a typical depolarization mechanism as it relates to skeletal muscle contraction.

How are muscarinic ACh receptors different?

A

ACh binding to muscarinic receptors elicits intracellular response via GPCRs

These initiate a wide variety of responses and are generally slower than nicotinic responses

41
Q

_________ refers to the idea that there are drugs we take in daily life that cause plastic events in the brain, leading us to require those substances

A

Dependency

42
Q

Caffeine acts on ________ receptors in the neural membrane. This is a CNS neuromodulator that has specific receptors, when it binds to its receptors, neural activity slows down. It partially regulates sleep and dilates the blood vessels to provide appropriate oxygenation during sleep.

Caffeine binds to its receptors in a __________ fashion, and begins to speed up neural activity. It also causes the pituitary gland to secrete hormones that in turn cause the adrenal glands to produce more _________

A

Adenosine

Competitive

Adrenaline (epinephrine)

43
Q

The ___________ __________ is considered a special synapse where all muscle fibers are innervated by a single motor neuron, making it a motor unit

A

Neuromuscular junction

44
Q

What is a motor unit?

A

All muscle fibers are innervated by a single motor neuron, and branches of the motor neuron innervate a single muscle fiber

45
Q

At the neuromuscular junction, the end-plate sarcolemma folds internally, known as ________ _______

A

Junctional folds

46
Q

ACh synthesis:

_______ is transported into the cell by the plasma membrane transporter

_______-___ from mitochondria is combined with the above blank by the enzyme _________ __________

ACh is then imported into vesicles by the Vesicular ACh Transporter (VAT) which requires _____. At this point ACh concentration is ______

A

Choline

Acetyl-CoA; choline acetyltransferase

ATP; high

47
Q

Once ACh has been synthesized and stored, under what conditions will it be released? What is its effect?

A

Depolarization causes voltage-gated Ca channels (VGCCs) to open and calcium will enter the cell

It induces vesicle mobilization, docking, and fusion with the plasma membrane

48
Q

What are 2 specific proteins discussed in class that initiate docking and fusion of ACh vesicles to the plasma membrane following depolarization?

A

VAMP and SNAP25

49
Q

Once depolarization occurs, only 100-200 ACh vesicles might release content at a time depending largely on what 2 factors?

A

Signal “strength”

Cell type

50
Q

What are the 3 primary methods of ACh breakdown following a depolarization event?

A

Acetylcholinesterase degrades ACh

Reuptake into motor neuron + diffusion away from synapse

Vesicle endocytosis

51
Q

Acetylcholinesterase is an enzyme that breaks ACh down into what 2 components? Which of these components can be retaken into the motor neuron?

A

Choline + Acetate

Choline can be retaken into motor neuron

52
Q

Of the 2 types of ACh receptors: Nicotinic (ionotropic) and Muscarinic (metabotropic), which one is not found at the neuromuscular junction?

A

Muscarinic

53
Q

Skeletal muscle contraction via neuromuscular junctions occurs using what type of ACh receptor?

A

Nicotinic (ionotropic)

54
Q

Skeletal muscle contraction requires nicotinic receptors at the NMJ. What types of muscle utilize muscarinic (metabotropic) receptors?

A

Smooth muscle contraction

Cardiac muscle = decreased HR and conduction velocity (SA node, AV node, atrium, and ventricle)

55
Q

The cellular response via muscarinic ACh receptors takes seconds. There are 5 subtypes of muscarinic receptors in mammals. Which ones are found in the CNS, heart, and smooth muscle?

A

CNS = M1, M4, M5

Heart = M2

Smooth muscle = M3

56
Q

Nicotinic ACh receptors are _______-gated ion channels, typically for sodium

The cellular response takes milliseconds. The receptor is composed of 4 different subunits arranged in a pentamer. What are these subunits and which one(s) does ACh bind to?

A

Ligand

2 alpha subunits
1 beta subunit
1 delta subunit
1 gamma subunit

2 molecules of ACh bind to areas between alpha subunits and adjacent subunits

57
Q

The selectivity of ion passage through nicotinic ACh receptors depends on what?

What ions are nicotinic ACh receptors selective for?

A

The amino acids lining the pore – aspartic acid and glutamic acid (negatively charged)

These are selective for Na+, Ca2+, and K+

58
Q

There are various subtypes of nicotinic ACh receptors. The muscular subtype typically contains alpha, beta, delta, gamma, and epsilon subunits.

What subunits may be contained in neuronal subtypes of nicotinic ACh receptors?

A

Alpha and beta subunits, or alpha subunits only

59
Q

What are the steps to synaptic transmission at the NMJ?

A
  1. Action potential propagated at motor neuron
  2. Opening of voltage-gated calcium channels
  3. Ca influx - increased Ca levels
  4. Release of ACh
  5. ACh diffuses across synaptic cleft and binds nAChRs
  6. nAChRs open - sodium influx, local membrane potential changes
  7. Activation of VG sodium channels, larger membrane potential changes, depolarization/action potential
  8. ACh breakdown

MSK Exam II (20 decks)

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