Neuromuscular Junction - Smith Flashcards
How does the nervous system communicate with muscle?
via nueromuscular junctions
Are NM junctions and synapses similar in structure/function?
Yes
What ion diffuses across the muscle cell membrane to generate an action potential?
Na
Are motor end plates directly on muscle fibers?
yes
What does Sherington’s Law describe about the relationship of flexor/extensor muscles in a reflex arc?
when one set of muscles is activated, the opposing set is inhibited
Describe the process of events that occur when a reflex is triggered?
- Hammer hits knee, stretching tendon and sensory fibers in the tendon
2 A. Sensory neurons synapses/excites motor neuron in the spinal cord
2 B. Sensory neuron synapes with spinal interneuron, which activates an inhibitory neuron to flexor muscles - Motor neurons cause extensor contraction
3B. flexor muscles relax due to inhibition
Describe the shape of the action potential from a sensory neuron
Sharp, tall, positive depolarizing peak
Describe the shape of the action potential from an internueron?
sharpt, tall, positive depolarizing peak
Describe the shape of the action potential from an EPSP (extensor muscle in reflex)?
Long, broad, positive depolarizing peak
Describe the shape of the action potential from an IPSP (flexor muscle in reflex)?
long, broad NEGATIVE, HYPERPOLARIZING peak
what do Renshaw cells do?
they are inhibitory interneurons
Where are Renshaw cells found?
gray matter of spinal cord
What cells does Clostridium tetani act on?
Renshaw cells
What is the cause of death from strychnine?
Muscular convulsions leading to asphyxia via sheer exhaustion
How do Renshaw cells alter AP’s to cause inhibition?
Renshaw cells are interneurons, so when one neuron fires an AP, the Renshaw cell will fiber numerous AP’s in succession, releasing a TON of glycine and inhibiting the other motor neurons.
Where are the cell bodies of motor neurons located?
Brainstem or spinal cord
What are the parts of a motor unit?
- Motor neuron
2. All the muscle fibers it innervates
T/F? The motor neurons axons are myelinated and large in diameter.
TRUE
T/F? Once an alpha motor neuron is activated to produce an action potential, all of the fibers innervated by this neuron are activated and contract simultaneously.
TRUE
T/F? Each motor unit is made up of one type of muscle fibers: i.e., slow twitch, fast-twitch fatigable or fast-twitch fatigue resistant.
TRUE
What is the EPSP equivalent for the motor end plate?
End Plate Potential (EPP)
When does a motor end plate generate an AP?
When it reaches threshold.
Do the EPP and AP work by the same mechanisms?
NO
does the motor end plate, once stimulated, always fire an action potential?
YES
Is there a summative mechanism in motor end plates to generate an action potential?
No, it’s either all or none
Is EPP always supra-threshold?
YES
What is the effect of curare on EPP with respect to its threshold?
It takes the EPP from suprathreshold (firing an AP) to sub threshold (no AP and therefore no muscle contraction)
Where does curare act at the nueromuscular junction?
ACh receptors in the muscle membrane
What ions flow and in which directions do they flow at the neuromuscular junction?
Na into muscle
K out of muscle
A subthreshold EPP is identical to a (blank)
spontaneous MEPP (miniature end plate potential)
The single quanta which causes the MEPP is equivalent to the release of one (blank)
ACh vesicle
The release of numerous ACh vesicles from the neuron causes (blank) at the muscle
EPP
What is the “safety factor” of the neuromuscular junction?
the AP created by the neuron is always sufficient to create a EPP and muscle contraction
What kind of receptor does ACh bind to on the muscle cell?
Nicotinic
What does ACh esterase break down ACh into?
Acetate and choline
What is the fate of the acetate from ACh
broken down in the blood
what is the fate of the choline from ACh?
it is recycled into the neuron
Are MEPPs calcium dependent?
NO
Is the EPP calcium dependent
yes!
What is the effect of AChE blocking drugs (prostigmine)?
They increase the amplitude and duration of the EPPs
Do AChE blockers (prostigmine) alter MEPP frequency? What does this indicate about the way MEPP’s work?
NO. it means each MEPP is due to a QUANTAL PACKET (vesicular release) of ACh.
Describe the five steps of transmission across the NMJ?
- An action potential arrives at the end of a motor neurone, at the neuromuscular junction.
- Depolarization causes Ca2+ entry into nerve terminal and vesicle mobilization.
- This causes the release of the neurotransmitter acetylcholine.
- Acetycholine diffuses across synaptic cleft and binds to nicotinic receptor on sarcolemma.
- Activation of nicotinic receptors generates EPP.
The AP is carried into the muscle by invaginations in the cell membrane called (blank)
T-tubules
The action potential causes depolarization of T-tubule membrane that opens (blank) receptor on the sarcoplasmic reticulum.
ryanodine
Activation of ryanodine receptors leads to the store release of (blank) ions into the myofibrils.
calcium
Ca2+ causes (blank) to be displaced uncovering myosin binding sites on actin.
tropomyosin
(blank) cross bridges can now attach and the cross bridge cycle can take place.
myosin
(blank) ion based action potential depolarizes T-tubule membranes
Na
Ca channels, aka (blank) receptors, are stimulated by the Na depolarization to change ryanodine receptor confirmation
dihydropyridine
ryanodine receptors release calcium from what structure?
sarcoplasmic reticulum or ER
Ryanodine receptors are concentrated in what tissue type?
Skeletal muscle
T-tubules transmit signals from the sarcolemma to the (blank)
sarcoplasmic reticulum
organophosphates act by blocking what enzyme?
ACh esterase
What is the acronym to remember organophosphate poisoning?
SLUDGE: salivation, lacrimation, defecation, urination, GI upset, emesis
Bungarotoxin from cobra venom causes paralysis how?
by IRREVERSIBLY binding to ACh receptors in muscle, causing paralysis and death
What other ion actively competes with Ca at the NMJ?
Mg
How does black widow toxin lead to paralysis?
By causing a massive release and subsequent depletion of ACh
Botulinum toxin and tetanus prevent the release of (blank)
quanta
In Lambert-Eaton syndrome, antibodies bind to the (blank) on the presynaptic terminal?
calcium channels
Are the amplitudes of EPPs changed in Lambert Eaton syndrome?
Yes, they are reduced
Are the amplitudes of MEPPs changed in Lambert Eaton syndrome? What does this tell us about the role of MEPPs with regard to presynaptic calcium?
NO, they are normal! MEPP are NOT DEPENDENT on calcium!
Myasthenia gravis effects what part of the NMJ?
the muscle nicotinic receptors
After repetitive nerve stimulation, Myasthenia gravis patients show increased (blank)
fatigue and decreased signal amplitude
Are the MEPPs the same between normal people and people with myasthenia gravis?
No, pt’s with MG have smaller MEPPs.
Vesicle synaptic proteins bind the vesicle the pre or post synaptic membrane?
PREsynaptic!
Botulinum toxin acts on what proteins?
Cleaves vesicle synaptic proteins
What is the effect of botulinum toxin on nerve signaling?
It reduces the release of ACh
(blank) has also been associated with clean wounds, surgical procedures, insect bites, dental infections, and intravenous drug use.
Tetanus
Tetanus prevents release of (blank) from Renshaw cells
glycine! and GABA
The type of paralysis caused by tetanus is flaccid or spastic?
Spastic
the type of paralysis caused by botulinum is flaccid or spastic?
Flaccid
What are the three proteins botulinum cleaves?
- Synaptobrevin
- syntaxin
- SNAP-25
What protein does tetanus cleave?
synaptobrevin