Physiology: NMJ

Question 1

List and explain in sequence the steps involved in neuromuscular transmission in skeletal muscle and point out the location of each step on a diagram on NMJ.

Answer 1

1. Action potential comes to the NMJ.
2. Opening of voltage gated Ca2+ channel.
3. Influx of Ca2+ causes binding of vesicles to presynaptic membrane and causes exocytosis, which is caused by synapsin 1.
   - Ca2+ phosphoralates synapsin I and causes it (transmitter) to be removed from the vesicles.
4. Ach binds to receptor of the postsynaptic cell.
5. Ach is broken down by acetylcholinesterase.
6. Choline is transferred back into the axon terminal to make more ACh.

Question 2

Discuss the 4 steps in which SNARE proteins are involved in transmitter release.

Answer 2

1. Vesicle moves to the active zone.
2. Several protein participate by attaching vesicle to active zone.
3. SNARE proteins docks the vesicle to the membrane
4. Fusion of vesicle and membrane required an increase in intracellular Ca2+. Ca2+ binds to synaptogamin, permitting fast fusion between the vesicle and membrane.

Question 3

Explain the concepts of quantal release.

Answer 3

Quantal release is the amount of neurotransmitter contained within the vesicles. These are released due to the change in the membrane potential of a muscle cell.

Question 4

Explain the concepts of receptor reserve.

Answer 4

A percentage of receptors that must be blocked before any effect on the muscle can take place.

Note:
A receptor must be occupied by 75% in order for a muscle contraction to take place.

Question 5

Describe the location, structure and receptor subtypes of the acetylcholine receptor and their associated second messenger systems.

Answer 5

1. Receptor - Nicotinic
2. Location - post synaptic cell
3. Structure - Rosette form
4. Subtypes- 5 subunits. (2 alpha. 1 beta, 1 delta, 1 epsilon)
5. Associated 2nd messenger systems - ACh or exogenous agonist. (Need for all or none opening)

Question 6

List the possible sites for blocking neuromuscular transmission in the skeletal muscle.

Answer 6

Presynaptically - inhibit ACh synthesis and release
Postsynaptically - inhibiting ACh from binding to NM receptor.

Question 7

Give an example of an agent that could cause neuromuscular transmission blockage at each site.

Answer 7

Non - Depolarizing - Tubocurarine
Depolarizing - Succinylcholine

Question 8

Compare and contrast depolarizing blockade of the neuromuscular junction with non-depolarizing blockade.

Answer 8

1. Non- Depolarizing blockade involves the blocking of the NM receptor. No depolarization. Competes with ACh to prevent EPP from being large enough to activate a muscle contraction.
2. Depolarizing blockage involves acting as agonist at the NM receptor. Depolarizes skeletal muscle. Prolong can causes paralysis

Question 9

List examples of common drugs used in neuromuscular blockade.

Answer 9

Non - Depolarizing - Curare.

Depolarizing - Succylncholine

Question 10

Explain the depolarizing blockade.

Answer 10

1. Agonists NM receptor
2. Fasciculation and twitches seen on onset.
3. Over use (prolong depolarization) can cause paralysis
4. No more action potentials.
5. Resistant to achytehcholinesterase.

Question 11

Discuss the physiological principles involved in myasthenia gravis.

Answer 11

1. Antibodies affect the ACh receptor by decreasing the amount of receptors on the end plate and reducing postsynaptic membrane folds.

Question 12

Discuss the physiological principles involved in Eaton Lambert syndrome. (LEMS)

Answer 12

1. Autoimmune disease that results in the non functioning of Ca2+ channels on the NMJ membrane.
2. The non working channels prevents ACh from leaving the cells.
3. Results in ACh not targeting muscles to contract this causing weakness.

Question 13

Discuss the physiological principles involved in malignant hyperthermia.

Answer 13

1. Triggered by anesthetics and neuromuscular agents.
2. Caused by a defect in the ryanodine receptor.
3. An uncontrolled amount of Ca2+ is released from the SR thus causing contracture and increase in body temperature.

Question 14

Discuss the clinical presentation of myasthenia gravis.

Answer 14

1. Fluctuating weakness
2. Head flexion and exertion weakness
3. Extra ocular muscle weakness

Question 15

Discuss the role of Dantrolene in Malignant hyperthermia.

Answer 15

It blocks the inappropriate response of ryanodine receptor and prevents Ca2+ loss.
Decreases Ca2+ efflux from SR.

Question 16

A 55-year-old patient presents with fluctuating muscle weakness, particularly affecting the extraocular muscles, leading to ptosis and double vision. The weakness worsens with activity throughout the day and improves with rest. Based on the source material, what is the most likely diagnosis?
A) Eaton Lambert Syndrome
B) Malignant Hyperthermia
C) Myasthenia Gravis
D) Depolarizing Neuromuscular Blockade

Answer 16

C) Myasthenia Gravis

Clinical presentations:
Fluctuating muscle weakness
Extraocular muscle weakness - ptosis
Head extension and flexion weakness.

Question 17

A neurologist administers a short-acting medication to a patient suspected of having Myasthenia Gravis. The patient’s muscle weakness, including ptosis, transiently improves. According to the sources, what type of medication was likely administered, and how does it achieve this effect in this context?
A) A direct acetylcholine agonist, stimulating the few remaining receptors.
B) An acetylcholinesterase inhibitor, increasing acetylcholine concentration at the synapse.
C) A non-depolarizing blocking agent, competitively inhibiting acetylcholine.
D) A depolarizing blocking agent, causing prolonged depolarization.

Answer 17

B) An acetylcholinesterase inhibitor, increasing acetylcholine concentration at the synapse.

Question 18

A patient is undergoing surgery and requires muscle relaxation. The anesthesiologist administers a drug that acts as an agonist at the neuromuscular junction receptors, causing initial muscle fasciculations followed by paralysis. This drug is described as resistant to acetylcholinesterase breakdown. According to the sources, which drug prototype was most likely used?
A) Tubocurarine
B) Curare
C) Succinylcholine
D) Edrophonium

Answer 18

C) Succinylcholine

Clinical manifestation of ^:
Transient muscle fasciculations w/ paralysis
Bradycardia
Post operative pain
Resistant: acetylcholinesterase

Question 19

During a surgical procedure, a patient develops sudden fever, severe muscle rigidity, and a rapid heart rate after receiving an anesthetic and a neuromuscular blocking agent. The sources describe a rare hereditary disorder triggered by these agents. What is this condition called?
A) Myasthenia Gravis
B) Eaton Lambert Syndrome
C) Tetanus
D) Malignant Hyperthermia

Answer 19

D) Malignant Hyperthermia

Caused by a general anesthetic and neuromuscular agent

Question 20

In the condition described in the previous question, Malignant Hyperthermia, what is the underlying defect mentioned in the sources that leads to uncontrolled muscle contraction and heat generation?

A) Autoantibodies attacking the acetylcholine receptor.
B) Deficiency in acetylcholine synthesis enzymes.
C) A defect in the ryanodine receptor causing inappropriate calcium release from the sarcoplasmic reticulum.
D) Blockage of voltage-gated calcium channels in the presynaptic terminal.

Answer 20

C) A defect in the ryanodine receptor causing inappropriate calcium release from the sarcoplasmic reticulum.

Question 21

A drug is administered that blocks neuromuscular transmission by preventing acetylcholine from binding to its receptors at the motor end plate. This drug acts as an antagonist. The sources identify the prototype for this class of neuromuscular blocking agents. Which drug is this prototype?

A) Succinylcholine
B) Acetylcholine
C) Edrophonium
D) Tubocurarine

Answer 21

D) Tubocurarine

Tubocurarine — antagonist
Edrophonium — an inhibitor for Acetylcholisterease
Succinylcholine — agonist

Question 22

A patient requires intubation for a short diagnostic procedure. The anesthesiologist considers using a non-depolarizing neuromuscular blocking agent. The sources mention several drawbacks of the prototype non-depolarizing agent. Which of the following is listed as a drawback?

A) Causing bradycardia
B) Potentiation by acetylcholinesterase inhibitors
C) Release of histamine leading to hypotension
D) Very short duration of action

Answer 22

C) Release of histamine leading to hypotension

Tubocurarine:
Blocking of ganglia
Affects the muscarinic receptors
Effects is longer than 30 minutes
Release of histamine leading to hypotension, broncho- constriction and anaphylaxis

Question 23

According to the sources, neuromuscular transmission at the skeletal muscle junction involves the release of a specific neurotransmitter. What is this neurotransmitter? A) Norepinephrine
B) Serotonin
C) Acetylcholine
D) Dopamine

Answer 23

C) Acetylcholine

Question 24

In the process of neuromuscular transmission, acetylcholine is synthesized in the axon terminal. The sources state that this synthesis requires two precursor molecules and an enzyme. Which enzyme is necessary for the synthesis of acetylcholine from choline and acetyl coenzyme A?
A) Acetylcholinesterase
B) Choline kinase
C) Choline acetyltransferase (CAT)
D) Acetyl CoA synthase

Answer 24

C) Choline acetyltransferase (CAT)

Acetylcholinesterase is used for the breakdown of Acetylcholine. CAT is for the production.

Question 25

Following its release into the synaptic cleft at the neuromuscular junction, acetylcholine's action is rapidly terminated. According to the sources, which enzyme is responsible for the rapid breakdown of acetylcholine? A) Choline acetyltransferase B) Acetylcholinesterase (AChE) C) Monoamine oxidase D) Synapsin I

Answer 25

B) Acetylcholinesterase (AChE)

Question 26

The sources describe the process of neurotransmitter release from synaptic vesicles. This process is triggered by the arrival of an action potential at the presynaptic membrane, leading to the opening of voltage-gated channels and the influx of a specific ion. Which ion influx is crucial for triggering synaptic vesicle binding and exocytosis? A) Sodium (Na+) B) Potassium (K+) C) Calcium (Ca2+) D) Chloride (Cl-)

Answer 26

C) Calcium (Ca2+)

Question 27

The sources mention that Botulinum and Tetanus toxins act to prevent synaptic vesicles from releasing their neurotransmitter content. Based on the described mechanism of acetylcholine release, which specific process are these toxins likely interfering with? A) Synthesis of acetylcholine B) Reuptake of choline C) Breakdown of acetylcholine in the cleft D) Binding of vesicles to the presynaptic membrane or fusion (mediated by proteins like SNAREs)

Answer 27

D) Binding of vesicles to the presynaptic membrane or fusion (mediated by proteins like SNAREs) Note: They inhibit the synaptic vesicles from releasing their neurotransmitter content.

Question 28

The amount of neurotransmitter contained within a single synaptic vesicle is referred to by a specific term in the sources. What is this term? A) Miniature end-plate potential (mEPP) B) Quantum C) End-plate potential (EPP) D) Synaptic load

Answer 28

B) Quantum

Question 29

A miniature end-plate potential (mEPP) represents the change in membrane potential produced by the release of a single quantum of acetylcholine. The sources state that a normal end-plate potential (EPP), produced by stimulation of the entire nerve, is significantly larger than an mEPP. How much larger is a typical EPP compared to an mEPP, according to the sources? A) Approximately 2 times larger B) Approximately 10 times larger C) Approximately 100 times larger D) Approximately 1000 times larger

Answer 29

C) Approximately 100 times larger

Question 30

A patient receiving a non-depolarizing neuromuscular blocking agent (like Tubocurarine) requires careful monitoring. The sources mention the concept of "Receptor Reserve," where a certain percentage of receptors can be blocked before muscle contraction is affected. In which muscle groups is the Receptor Reserve described as being least? A) Muscles of respiration B) Large muscles of coarse movement C) Muscles of the face and eyes D) Muscles of the limbs

Answer 30

C) Muscles of the face and eyes RR is seen more in muscles of respiration and muscles of course movement

Question 31

The sources explain that Non-depolarizing neuromuscular blocking agents act by blocking the acetylcholine receptors at the motor end plate. What term is used to describe the action of these agents on the receptor? A) Agonist B) Partial Agonist C) Antagonist D) Allosteric Modulator

Answer 31

C) Antagonist Depolarizing is agonist

Question 32

A patient is given Succinylcholine. The sources describe that this drug depolarizes the skeletal muscle membrane. Why does prolonging this depolarization using an agonist drug prevent the return to the resting state and cause paralysis? A) It prevents the release of acetylcholine from the presynaptic terminal. B) It enhances the breakdown of acetylcholine by acetylcholinesterase. C) It prevents the muscle membrane from repolarizing, making it unresponsive to further impulses. D) It blocks the calcium channels necessary for muscle contraction.

Answer 32

C) It prevents the muscle membrane from repolarizing, making it unresponsive to further impulses.

Question 33

Succinylcholine causes a "Depolarizing Blockade." The sources describe two phases of this block. In Phase I block, the membrane remains depolarized, resulting in flaccid paralysis. How is the Phase I block affected by acetylcholinesterase inhibitors, according to the sources? A) It is reversed. B) It is unaffected. C) It is potentiated (enhanced). D) It is converted to Phase II block.

Answer 33

C) It is potentiated (enhanced). Curare — Reversed

Question 34

A patient has received Succinylcholine for muscle relaxation. After prolonged exposure, the muscle end plate repolarizes, but it cannot be depolarized as long as the drug is present. According to the sources, this state is referred to as which phase of depolarizing blockade? A) Phase 0 block B) Initial depolarization phase C) Phase I block D) Phase II block

Answer 34

D) Phase II block Phase 1 block involves membrane demoralization and remains that way w/ drug at attached, causing muscle cell to remain in rest state

Question 35

Myasthenia Gravis is described as an autoimmune disorder. The sources specify the target of the antibodies in this disease. What are these antibodies primarily directed against? A) Acetylcholinesterase enzyme B) Voltage-gated calcium channels C) Acetylcholine receptors at the neuromuscular junction D) Synapsin I protein

Answer 35

C) Acetylcholine receptors at the neuromuscular junction. The decrease the # of NMJ receptors, decreasing postsynaptic membrane and widening the cleft.

Question 36

Besides a decreased number of nicotinic acetylcholine receptors, what other morphological changes at the motor end-plate are mentioned in the sources as being characteristic of Myasthenia Gravis? A) Increased postsynaptic membrane folds and narrowed synaptic cleft. B) Increased size and number of synaptic vesicles. C) Reduced postsynaptic membrane folds and widened synaptic cleft. D) Accumulation of acetylcholinesterase in the synaptic cleft.

Answer 36

C) Reduced postsynaptic membrane folds and widened synaptic cleft.

Question 37

A patient with Myasthenia Gravis typically presents with fluctuating weakness. The sources provide specific details about how this weakness manifests over time. How does the weakness generally change throughout the day and with rest? A) It improves during the day and worsens with rest. B) It increases during the day and improves with rest. C) It remains constant throughout the day, unaffected by rest or exertion. D) It worsens with rest and improves with exertion.

Answer 37

B) It increases during the day and improves with rest.

Question 38

According to the sources, the use of neuromuscular blocking agents in clinical settings requires artificial respiration of the patient. Why is this necessary? A) The drugs cause severe pain requiring ventilation. B) They cause sedation that suppresses respiratory drive. C) They block muscarinic receptors affecting lung function. D) They cause paralysis of the respiratory muscles, including the diaphragm.

Answer 38

D) They cause paralysis of the respiratory muscles, including the diaphragm.

Question 39

Before the advent of reliable neuromuscular blocking agents, deep surgery often required very deep levels of anesthesia. What significant hazard of achieving muscle relaxation and reflex abolition solely through deep anesthesia is mentioned in the sources? A) Increased risk of awareness during surgery. B) Often led to patient death on the operating table. C) Caused irreversible damage to motor neurons. D) Resulted in severe post-operative pain.

Answer 39

B) Often led to patient death on the operating table.

Question 40

The sources state that Acetylcholine is made from choline and acetyl coenzyme (acetyl CoA) in the axon terminal. Where are these precursor molecules located? A) Exclusively in the synaptic cleft. B) Exclusively in the muscle fiber. C) Exclusively in the Schwann cell sheath. D) In the axon terminal (presynaptic terminal).

Answer 40

D) In the axon terminal (presynaptic terminal).

Question 41

The process of packaging neurotransmitter into synaptic vesicles is crucial for efficient release. Which step in the transmitter release pathway, as described in the sources, occurs after the opening of voltage-gated Ca2+ channels and Ca2+ influx? A) Arrival of the action potential at the presynaptic membrane. B) Binding of vesicles to the presynaptic membrane and exocytosis. C) Breakdown of acetylcholine in the synaptic cleft. D) Binding of acetylcholine to postsynaptic receptors.

Answer 41

B) Binding of vesicles to the presynaptic membrane and exocytosis.

Question 42

The sources mention that the influx of Ca2+ leads to the binding of vesicles to the presynaptic membrane and exocytosis. This is believed to be mediated, in part, by the protein synapsin I. How does Ca2+ influence synapsin I to facilitate vesicular exocytosis? A) Ca2+ directly activates synapsin I to bind vesicles. B) Ca2+ phosphorylates synapsin I (via a calmodulin-mediated protein kinase), causing it to be removed from synaptic vesicles. C) Ca2+ inhibits the action of synapsin I. D) Synapsin I is a calcium channel, and its opening releases calcium.

Answer 42

B) Ca2+ phosphorylates synapsin I (via a calmodulin-mediated protein kinase), causing it to be removed from synaptic vesicles.

Question 43

The sources state that neuromuscular blockade can occur at several sites. Which of the following is listed as a possible site for blocking neuromuscular transmission? A) Within the muscle fiber sarcoplasmic reticulum. B) In the central nervous system, inhibiting motor neuron firing. C) Presynaptically, inhibiting ACh synthesis or release. D) Within the axon, blocking action potential propagation.

Answer 43

C) Presynaptically, inhibiting ACh synthesis or release. And Postsynaptically inhibiting the binding of ACh to its receptor

Question 44

The sources compare Non-depolarizing and Depolarizing blocking agents. How do Depolarizing blocking agents primarily act at the neuromuscular receptors? A) As antagonists, blocking the receptor site. B) As agonists, activating the receptor. C) By destroying the receptor. D) By preventing neurotransmitter synthesis.

Answer 44

B) As agonists, activating the receptor.

Question 45

When administering Succinylcholine, the sources mention an initial visible effect on the muscle. What is this initial effect observed at the onset of depolarizing blockade? A) Complete flaccid paralysis immediately. B) Enhanced muscle strength. C) Fasciculation and twitches (transient muscle fasciculations). D) Sustained muscle rigidity (contracture).

Answer 45

C) Fasciculation and twitches (transient muscle fasciculations).

Question 46

The sources note that the dose-response curves for Non-depolarizing blocking agents are very steep. Despite this, there is a period of declining force for the muscle as a whole before complete paralysis. Why does this happen? A) The drug must first be metabolized before it can act. B) Not every neuromuscular junction fails at the same dose/point. C) The drug causes muscle fatigue independent of receptor blockade. D) Muscle fibers have varying numbers of acetylcholine receptors.

Answer 46

B) Not every neuromuscular junction fails at the same dose/point.

Question 47

According to the sources, what is the primary function of the protein synaptotagmin in the process of transmitter release? A) It synthesizes acetylcholine. B) It breaks down acetylcholine in the cleft. C) It binds Ca2+ and permits fast fusion of the vesicle membrane with the plasma membrane. D) It reuptakes choline into the presynaptic terminal.

Answer 47

C) It binds Ca2+ and permits fast fusion of the vesicle membrane with the plasma membrane.

Question 48

The sources mention that Malignant Hyperthermia is treated with Dantrolene. How does Dantrolene interfere with the process responsible for Malignant Hyperthermia symptoms? A) It blocks the acetylcholine receptor. B) It inhibits acetylcholinesterase. C) It interferes with excitation-contraction coupling by decreasing calcium efflux from the sarcoplasmic reticulum. D) It increases calcium sequestration into the sarcoplasmic reticulum.

Answer 48

C) It interferes with excitation-contraction coupling by decreasing calcium efflux from the sarcoplasmic reticulum.

Question 49

According to the sources, what is the origin of the cell body of a motor neuron? A) Peripheral ganglia B) Ventral horn of the spinal cord C) Dorsal root ganglia D) Cerebellum

Answer 49

B) Ventral horn of the spinal cord

Question 50

The sources mention that Myasthenia Gravis weakness may be worse in certain muscle groups. While extraocular and facial muscles are commonly affected early, which other muscle group is noted as potentially having worse weakness? A) Distal muscles B) Muscles of the trunk C) Proximal muscles D) Smooth muscles

Answer 50

C) Proximal muscles

Question 51

The sources note that Tubocurarine affects muscarinic receptors. What specific effect on heart rate is mentioned as a potential consequence of this muscarinic receptor effect? A) Bradycardia B) Tachycardia C) Arrhythmia D) No effect on heart rate

Answer 51

B) Tachycardia It affects the parasympathetic effect of heart rate

Question 52

When considering the clinical use of neuromuscular blocking agents, the sources explicitly state that these drugs do not cause sedation or relief of pain. What does this imply about their use in surgery? A) They can be used as a sole anesthetic agent. B) They eliminate the need for anesthetic agents. C) They must be used in conjunction with agents that provide sedation and analgesia. D) They are adjuncts and require other medications for anesthesia and pain control.

Answer 52

They are adjuncts and require other medications for anesthesia and pain control.

Question 53

The sources briefly mention SNARE proteins in the context of transmitter release. What general function are SNARE proteins associated with in this process? A) Synthesizing neurotransmitter. B) Breaking down neurotransmitter. C) Packaging neurotransmitter into vesicles. D) Facilitating vesicle fusion with the presynaptic membrane.

Answer 53

D) Facilitating vesicle fusion with the presynaptic membrane.