Neuromuscular Junction

Front 1

What is the function of the neuromuscular junction?

Back 1

Allows nerves to precisely activate muscles to facilitate proper movement.

Front 2

What is the corticospinal tract?

Back 2

Most common UMN (upper motor nerve) pathways.

1. signal travels from motor cortex to spinal cord.
2. signal activates LMN (lower motor nerves) known as anterior horn cells
3. AHCs send signal to NMJ
4. signal stimulates VGCC (voltage-gated Ca channel)
5. influx of calcium
6. Ca triggers ACh release
7. ACh binds to post-synaptic nicotinic receptors.

Front 3

What does influx of calcium in the NMJ trigger?

Back 3

Triggers ACh containing vesicles to bind to presynaptic terminals.

Front 4

How is ACh synthesized?

Back 4

Synthesized from acetyl coenzyme A and choline by choline acetyltransferase (CAT)

Front 5

What does synapsin do?

Back 5

Ties together ACh vesicles by cross linking them to each other and to actin filaments.

Front 6

What does calcium entry into the presynaptic terminal cause in terms of proteins?

Back 6

Phosphorylation of CaMKII (calcium/calmodulin-dependent protein kinase type II); this breaks the connection b/e synapsin and the vesicles which are then free to bind to the presynaptic terminal.

Front 7

What must calcium bind to in order for the fusion of ACh vesicles to the presynaptic terminal to occur?

Back 7

Synaptotagmin

Front 8

What is synaptotagmin?

Back 8

A protein found w/in the membrane of the vesicle.

Front 9

What does binding of synaptotagmin lead to fusion of?

Back 9

The four SNARE proteins:

1. Synatobrevin
2. Syntaxin
3. Two SNAP-25 proteins

Front 10

Where are SNAP-25 and syntaxin proteins found?

Back 10

In the plasma membrane of the presynaptic terminal

Front 11

Where is synatobrevin found?

Back 11

In the membrane of the vesicle

Front 12

What proteins must fuse in order for ACh to be released?

Back 12

The four SNARE proteins: (synatobrevin, syntaxin and the two SNAP-25 proteins)

Front 13

What are boutons?

Back 13

The bulb-shaped endings that contact muscle

Front 14

What are postjunctional folds?

Back 14

Infoldings of the muscle fibers that increase the surface area of the muscle membrane

Front 15

Where are the N1 receptors located?

Back 15

On the crest of the motor end plate, midway along the length of the muscle fiber.

Front 16

What region of the N1 receptor does ACh bind to?

Back 16

the alpha-subunits

Front 17

What happens when the motor end-plate is depolarized to ~-50mV?

Back 17

A end-plate potential results

Front 18

How are most NTs deactivated?

Back 18

By reuptake into the presnynaptic terminal

Front 19

How is ACh primarily inactivated?

Back 19

By acetylcholineesterase (AChE); located in the synaptic cleft

Front 20

What is the general description of Lambert-Eaton syndrome?

Back 20

A paraneoplastic syndrome (a disease that is caused by cancer in the body) that results in a defect of neuromuscular transmission.

Front 21

What is the pathophysiology of lambert-eaton syndrome?

Back 21

An autoimmune response against the presynaptic terminal of the NMJ.

Front 22

What is the etiology of lambert-eaton syndrome?

Back 22

Antigenic similarity b/e the tumor (usually small cell lung cancer) and the presynaptic terminal results in formation of Abs against presynaptic VGCCs

Front 23

What causes the clinical symptoms of LES?

Back 23

Reduced stimulation of both nicotinic and muscarinic receptors

Front 24

What is the trade-mark, classic, symptom of Lambert-Eaton syndrome?

Back 24

Brief sustained muscle action may result in a transient increase in strength. In addition, reflexes may briefly return after muscle activation.

Front 25

A pt walks into your clinic. He is 42 yo and has a 40 pack year smoking hx. While walking into the examination room the patient stumbles often and is unsteady as he walks. During the history he complains of dry-mouth and asks for a cup of water. During the examination he has bilateral absence of the patellar reflex, you ask him to abduct his thigh repeatedly. After he finishes the movement you try his patellar reflex again and it is there. What's the diagnosis? What is the etiology? What should you look for?

Back 25

Dx: Lambert-Eaton Syndrome
Et: Abs made against VGCCs
Look EXTENSIVELY for small cell lung carcinoma

Front 26

What is the pathophysiology of myasthenia gravis?

Back 26

Circulating Abs degrade and destroy postsynaptic nicotinic acetylcholine receptor sites, impairing synaptic transmission

Front 27

Despite the fact that myasthenia gravis is "the great imitator" what symptoms are a classic feature of MG?

Back 27

Symptoms that occur w/ fatigue

*i.e. If you have the pt. look up at the ceiling for 2-3 minutes and after a short-while their eye-lids droop would indicate MG

Front 28

Why are sensation and reflexes normal in pts w/ MG?

Back 28

B/c the disease is caused by Abs against NMJ N1 receptors. So sensation and reflexes are normal b/c the UMNs, LMNs and sensory peripheral nerves are all uninvolved

Front 29

What is the most common symptom of pts w/ MG? second? third?

Back 29

1. Ocular weakness
2. episodic dysarthria (slurred speech) and dysphagia (difficulty swallowing)
3. eventually most pts develop extremity weakness.
*ALL symptoms are more likely to occur w/ fatigue.

Front 30

What is tensilon?

Back 30

A AChE inhibitor

Front 31

A patient walks into your clinic. During the hx he tells you he has been to 2 other doctors who have been unable to dx his prob. During the examination you ask the pt. to raise his eyes and look at the ceiling for 3 minutes. After 2 minutes of this his eyelids droop and he begins to get a tired gaze. What's the Dx? What is the Et? What else should you look for? What medicine should you give/what procedure should be conducted?

Back 31

Dx: Myasthenia gravis
Et: Abs against N1 receptors in NMJ
Look for thymomas
Rx: Tensilon and a thymectomy

Front 32

What is botulism?

Back 32

A rare but sometimes fatal paralytic disease that is caused by spores from the bateria C. Botulinum.

Front 33

How does botulism cause paralysis?

Back 33

By binding to axon terminals and disrupting cholinergic transmission by cleaving specific SNARE proteins.

This prevents fusion of the ACh-containing vesicles, so ACh is never released and the muscles are not stimulated.

Front 34

What is the progression of symptoms in botulism?

Back 34

RAPID

1. Occular weakness
2. bulbar muscles (dysphagia and dysarthria)
3. muscle weakness

Front 35

What branch of the nervous system does botulism involve? why?

Back 35

Only the peripheral nervous system.

B/c the toxins cannot cross the B-B-B.

Front 36

A patient comes into your clinic. During the hx you discover that he has recently returned from tijuana last week where he partied hard and experimented w/ black-tar heroine. During the examination you notice he has ptosis and ocular weakness. His speech is slurred and he complains of dysphagia. His pupils are dilated. What's the dx? et? treatment?

Back 36

dx: botulism
et: spore toxins bind to presynaptic terminals and cleaves the SNARE proteins, preventing vesicle fusion and ACh release.
treatment: Mechanical ventilator, gastric lavage, antibiotics (penicillin G) and antitoxin

Front 37

What is the effect of Black Widow Spider Toxin?

Back 37

Triggers a massive exocytosis from presynaptic terminals.

Results in muscle spasms and cramps.

Front 38

What is the effect of organophosphate exposure?

Back 38

Cause irreversible inhibition of AChE, resulting in excessive stimulation of nicotinic and muscarinic receptors.

Front 39

A pt. walks into your clinic. He is a 48 yo mexican laborer on a strawberry field outside Monterey. He describes having terrible diarrhea, nausea and vomiting. While checking his pulse you notice he is experiencing tachycardia. He is also very anxious and fatigued. What's the dx? what is the Et? What is the Rx?

Back 39

Dx: Organophosphate exposure
Et: OPs cause irreversible inhibition of AChE, resulting in excessive stimulation of nicotinic and muscarinic receptors.
Rx: Atropine

Front 40

What does atropine do?

Back 40

Competes w/ ACh for muscarinic receptors. Ineffective at treating NMJ disorders though, because it doesn't bind to nicotinic receptors

Front 41

What is succinylcholine? what is its mechanism of action?

Back 41

The only depolarizing blocker available in the US and is used exclusively to relax muscles during intubation.

Succinylcholine binds to ACh receptors, initially causing a series of APs. Overstimulation causes the receptor to inactivate and close.

Front 42

A patient is carried into your clinic while you are on a mission trip to Taiwan. His friends say he has been bitten by a cobra. What is the Dx? Et? Mech?

Back 42

Dx: beta-bungarotoxin from cobra bite
Et/Mech: blockage of NM transmission by binding tightly to ACh receptor and overstimulating then closing it.

Front 43

A 28 yo spy is stumbles into your hotel room while you are on vacation in budapest. After looking into your eyes for a minute he weakly mutters "help...". You pull a spy-dart from his neck just as the phone rings, a voice with a british accent asks for your help to save Agent Bond. What's the dx? mech? what form of this toxin is used outside the US as an anesthetic?

Back 43

Dx: shot with a curare dart
Mech: Curare competitively competes w/ ACh for N1 receptors, decreasing the size of the EPP resulting in muscle weakness.
*Tubocurarine is sometimes used as an anesthetic