Pharm Of NMJ

Question 1

What are the steps involved in NMJ neurotransmission

Answer 1

1. Axonal conduction
2. Junctional transmission
3. ACh signaling
4. Muscle contraction

Question 2

What are the steps of junctional transmission?

Answer 2

1. ACh synthesis
2. ACh storage
3. ACh release
4. ACh destruction

Question 3

What is choline acetyltransferase?

Answer 3

It is an enzyme that combines acetyl coenzyme A and choline to form ACh

Question 4

What happens in ACh synthesis?

Answer 4

Choline transporter transports choline into the cell and then ChAT catalyzes the reaction to make ACh

Question 5

Patients with alzheimers disease have a reduction in which enzyme from this process?

Answer 5

Choline acetyltransferase

Question 6

What happens in ACh storage?

Answer 6

ACh vesicular transporter shuttles ACH into storage vesicles after ACH synthesis. ATP dependent

Question 7

What happens in ACh release?

Answer 7

Voltage gated calcium channels open upon depolarization and allow calcium to enter the cell. Calcium promotes vesicle membrane fusion.

Then the proteins VAMP and SNAPs initiate vesicle-plasma membrane fusion and release of ACh

Question 8

What happens in ACH destruction?

Answer 8

Acetylcholinesterase cleaves ACh into choline and acetate.

Choline is recycled back into the motor neuron via choline transporter

Question 9

What receptors does ACh activate on the muscle cell?

Answer 9

Nicotinic and muscarinic

Question 10

What are nAChRs activated by?

Answer 10

ACh and nicotine

Question 11

What are mAChRs activated by?

Answer 11

ACh and muscarine

Question 12

Where are nicotinic receptors found?

Answer 12

Only skeletal muscles

Question 13

Where are muscarinic receptors found?

Answer 13

Smooth muscle, cardiac muscle

Question 14

What type of receptor is mAChR?

Answer 14

G-couple protein receptor

Question 15

What type of receptors are nAChRs?

Answer 15

Ligand gated ion channels

Question 16

What does tetrodotoxin do?

Answer 16

Inhibits the voltage gated sodium channels to block axonal conduction

Causes weakness, dizziness, parasthesias, paralysis, death due to respiratory failure

Question 17

How do anesthetics affect the nerve action potential?

Answer 17

They inhibit voltage gated sodium channels.

Question 18

What does botulinum toxin do?

Answer 18

Cleaves components of the core SNARE complex involved in exocytosis, preventing the release of ACh

Question 19

How does tetanus toxin affect vesicular ACh release?

Answer 19

Blocks the fusion of synaptic vesicles by targeting synaptobrevin

Causes spastic paralysis (locked jaw, restlessness, stiff neck, rigid abdomen)

Question 20

What do neuromuscular blocking drugs do?

Answer 20

Agonists and antagonists of the nAChR can prevent synpatic transmission

Agonists activate the receptor to signal as a direct result of binding to it and antagonists bind to receptors but do not activate generation of a signal

Question 21

What do curare alkaloids do?

Answer 21

Compete with ACh for the nAChR on the motor end plate, decreasing the size of the EPP

Leads to flaccid paralysis of skeletal muscle (used during anesthesia to relax); paralysis reversed by increasing ACh in the NMJ

Question 22

What does succinylcholine do?

Answer 22

Depolarizes neuromuscular blocker that binds to skeletal muscle nAChR and initially causes depolarization (acts as an agonist); continued depolarization leads to receptor blockade and paralysis

Used as an induction agent for anesthesia

Question 23

What do cholinesterase inhibitors do?

Answer 23

Bind to AChE and block its enzymatic activity; increases the concentration of ACh at the NMJ

Question 24

What does dantrolene do?

Answer 24

Inhibits ryanodine receptors in the sarcoplasmic reticulum and blocks release of calcium; used to treate malignant hyperthermia (spasticity associated with upper motor neuron disorders)