Pharm Of NMJ Flashcards
What are the steps involved in NMJ neurotransmission
- Axonal conduction
- Junctional transmission
- ACh signaling
- Muscle contraction
What are the steps of junctional transmission?
- ACh synthesis
- ACh storage
- ACh release
- ACh destruction
What is choline acetyltransferase?
It is an enzyme that combines acetyl coenzyme A and choline to form ACh
What happens in ACh synthesis?
Choline transporter transports choline into the cell and then ChAT catalyzes the reaction to make ACh
Patients with alzheimers disease have a reduction in which enzyme from this process?
Choline acetyltransferase
What happens in ACh storage?
ACh vesicular transporter shuttles ACH into storage vesicles after ACH synthesis. ATP dependent
What happens in ACh release?
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
What happens in ACH destruction?
Acetylcholinesterase cleaves ACh into choline and acetate.
Choline is recycled back into the motor neuron via choline transporter
What receptors does ACh activate on the muscle cell?
Nicotinic and muscarinic
What are nAChRs activated by?
ACh and nicotine
What are mAChRs activated by?
ACh and muscarine
Where are nicotinic receptors found?
Only skeletal muscles
Where are muscarinic receptors found?
Smooth muscle, cardiac muscle
What type of receptor is mAChR?
G-couple protein receptor
What type of receptors are nAChRs?
Ligand gated ion channels
What does tetrodotoxin do?
Inhibits the voltage gated sodium channels to block axonal conduction
Causes weakness, dizziness, parasthesias, paralysis, death due to respiratory failure
How do anesthetics affect the nerve action potential?
They inhibit voltage gated sodium channels.
What does botulinum toxin do?
Cleaves components of the core SNARE complex involved in exocytosis, preventing the release of ACh
How does tetanus toxin affect vesicular ACh release?
Blocks the fusion of synaptic vesicles by targeting synaptobrevin
Causes spastic paralysis (locked jaw, restlessness, stiff neck, rigid abdomen)
What do neuromuscular blocking drugs do?
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
What do curare alkaloids do?
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
What does succinylcholine do?
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
What do cholinesterase inhibitors do?
Bind to AChE and block its enzymatic activity; increases the concentration of ACh at the NMJ
What does dantrolene do?
Inhibits ryanodine receptors in the sarcoplasmic reticulum and blocks release of calcium; used to treate malignant hyperthermia (spasticity associated with upper motor neuron disorders)
