19. Pharmacology of the Neuromuscular Junction Flashcards
Which acetylcholine receptor is the primary receptor for skeletal muscle, and is not present on smooth and cardiac muscle?
Nicotinic acetylcholine receptor
Is a nicotinic acetylcholine receptor ionotropic or metabotropic (g-protien mediated)?
Ionotropic
What enzyme is responsible for acetylcholine synthesis from choline and acetyl CoA?
Choline acetyltransferase
What enzyme’s deficiency leads to decreased acetylcholine production in Alzheimer’s Disease?
Choline acetyltransferase
What two plasma membrane protiens assist in fusion of the vesicles to the plasma membrane of the axon terminus, resulting in the release of acetylcholine?
VAMPs and SNAPs
What does the influx of calcium into the axon terminus do?
Moves the acetylcholine containing vesicles closer to the plasma membrane.
Which act faster, muscarinic or nicotinic ACh receptor actions?
Nicotinic (milliseconds, vs seconds for muscarinic)
How do nicotinic ACh receptors select for positively charged ions to let through?
The inside of the receptor’s channel is coated with negative charges
What is the mechanism for Tetrodotoxin?
Inhibition of voltage gated sodium channels
What is the mechanism of action for local anesthetics?
Inhibition of voltage gated sodium channels
What is the mechanism of action for Botulinum Toxin?
Cleaves components of the SNARE complex, preventing ACh release
What are the symptoms of botulism?
Blurred vision,
descending bilateral cranial neuropathy,
nausea,
vomiting,
dry mouth
What is the mechanism of action of Tetanus Toxin?
Attacks synaptobrevin and prevents release of inhibitory neurotransmitters
What is the mechanism of action for the Curare Alkaloids like d-tubocurarine?
Non-depolarizing inhibitor of ACh
Competes with ACh and does not lead to an action potential
How would you reverse the effect of a Curare Alkaloid?
Increase the amount of ACh in the neuromuscular junction, eg via an acetylcholinesterase inhibitor
What is the mechanism of action for Succinylcholine?
Depolarizing neuromuscular blocker
Activates the nicotinic receptor via depolarization, and then doesn’t let them relax again - acheiving flaccid paralysis
(very short acting)
What is the mechanism of a cholinesterase inhibitor?
Binds to and inactivates acetylcholine esterase
What are cholinesterase inhibitors used for clinically?
Treatment of nerve gas and pesticide exposure
Myasthenia Gravis
Reversing neuromuscular blockade during anesthesia
What is the mechanism of action of Dantroline?
What is the use?
Ryanodine (RyR) inhibitor, stops muscle contraction by blocking calcium release
Treatment of malignant hyperthermia, since the elevation of body temperature is related to muscle contractions
