Pharmacology Flashcards
Are the branches of a motor neuron axon myelinated or unmyelinated as they reach the muscle?
motor neurone axon divides into unmyelinated branches near to the muscle
What is the name given to the terminal point of each branch of the motor neuron axon?
terminal bouton
forms a chemical synapse with the muscle membrane at NMJ
What does an AP travelling down the motor neuron axon to the terminal bouton cause?
release of the transmitter acetylcholine (ACh)
What cells surround the terminal bouton?
Schwann cells
What is the name given to the membrane of the motor end plate?
Sarcolemma
Where do synaptic vesicles of ACh wait until they are released?
Synaptic vesicles await release in clusters at active zones
WHat receptors are responsible for the uptake of ACh
Nicotinic ACh receptors
How is ACh synthesised?
Active transport of choline into terminal bouton
Choline + acetyl CoA = ACh
(mediated by Choline acetyl transferase enzyme)
ACH transported into vesicle
How is ACh released from the vesicles?
AP opens Ca channels on terminal bouton
Ca in terminal causes exocytosis of vesicles in active zones
What does ACh allow the nicotinic receptor to do?
Binds to specific binding sites which allow receptor to open
=> Na IN and K OUT
What enzyme is responsible for degradation of excess neurotransmitter in the synaptic cleft?
Acetylcholinesterase
Describe the structure of a nicotinic receptor
Pentamer
Subunits
- 2x alpha
- beta
- delta
- gamma
forms cation selective pore (=> positive ions flow through centre)
How is the end plate potential (e.p.p.) generated?
The driving force for Na+ > K+ at resting membrane potential
=> influx of Na+ > efflux of K+
=> depolarization known as the E.P.P
How is the amount of neurotransmitter in one vesicle defined?
each vesicle contains one ‘quantum’ of neurotransmitter
What occurs if an e.p.p exceeds threshold?
e.p.p that exceeds threshold triggers an ‘all or none’ propagated action potential that initiates contraction
What does the AP arriving at the T-Tubules induce?
Triggers release of Ca2+ from the SR
=> causes contraction by interacting with troponin associated with the myofibrils
What category of drugs are responsible for inhibiting AChE?
anti-cholinesterases - reversibly block action of AChE
What are the symptoms of Neuromyotonia (NMT, or Isaac’s syndrome) ?
cramps
stiffness
slow relaxation (myotonia)
muscle twitches (fasiculations)
What is thought to be the cause of Neuromyotonia?
autoimmune antibodies against voltage-activated K+ channels in the motor neurone
=> hyperexcitability (repetitive firing)
What treatments are usually given in neuromyotonia?
anti-convulsants (e.g. carbamazepine, phenytoin) which block voltage-activated Na+ channels
=> less Na influx to create e.p.p
Describe the common symptoms of Myasthenia Gravis
progressively increasing muscle weakness during periods of activity
weakness of the eye and eyelid muscles
What is the cause of Myasthenia Gravis
autoimmune antibodies against nicotinic ACh receptors in endplate
=> reduction in the number of functional channels and hence reduced amplitude of the e.p.p.
What treatments can be used for myasthenia gravis?
anticholinesterases (increase conc. of ACh in cleft)
- edrophonium for diagnosis
- pyridostigmine for long term Tx
immunosuppressant agents
- azathioprine
What is the cause of Botulinum Toxin?
exotoxin toxin (related to tetanus and diptheria)
- acts at motor neurone terminals to irreversibly inhibit ACh release
- enters presynaptic nerve terminal to enzymatically modify proteins involved in the docking of vesicles containing ACh (therefore preventing exocytosis)
