pharmacology of neuromuscular junction Flashcards
where are motor neurone cell bodies found
in either spinal cord or brain stream
how is skeletal muscle innervated
by motor neurons with myelinated axons
the motor neurone divides into unmyelinated branches near to the muscle, each branch innervates an individual skeletal muscle cells forming the motor unit
individual branches further divide into multiple fine branches each ending in a terminal bouton that forms a chemical synapse at the neuromuscular junction
what neurotransmitter is released at the neuromuscular junction
acetylcholine
where does the presynaptic terminal (buuton) synapse
at the endplate region of skeletal muscle fibres (post-synaptic)
what is the presynaptic terminal (bouton) surrounded by
Schwann cells
what is the synaptic cleft
small gap over which the neurotransmitter diffuses before encountering the nicotinic ACh receptors
where is the ACh released from
synaptic vesicles
where do vesicles queue up to release ACh
active zones
what is an overview of synaptic transmission in the neuromuscular junction
- synthesis of ACh
- storage of ACh by vesicles
- Release of ACh into synaptic cleft
- Receptor activation on the end plate
- transmitter inactivation
what is ACh synthesised from
choline and acetyl coA
What enzyme synthesises ACh
choline acyetyltranderase
what does arrival of the action potential at the pre-synaptic terminal cause
1) depolarisation and opening of Ca2+ channels
2) allows Ca2+ entry to the terminal
what does Ca2++ do at the pre-synaptic terminal
causes vesicles to fuse with presynaptic membrane (exocytosis) allowingg ACh to diffuse into the synaptic cleft
what does the ACh activate on the post synaptic end plate
nicotinic ACh receptors
how are nicotinic ACh receptors assembled
as a pentameter of glyocpotein subunits that surround a central pore.
The pore contains a gate that is closed in the absence of ACh but opens when to ACh molecules bind to the outside of the receptor.
what does the nicotinic ACH receptor do when its switched on
when gate is open Na+ enters the muscle cell, whilst K+ exits
the influx of Na+ is greater than the efflux of K+ therefore a depolarisation known as end plate potential is generated (Excess +ve charge makes the muscle depolarised (become less negative))
what is a miniature end plate potential
a tiny depolarisation of the end plate region caused by one quantum of transmitter being released from one vesicle
what forms the end plate potential
lots of miniature end plate potentials summated due to lots of vesicles releasing quantums of neurotransmitters at the same time
as long as the end plate potential is big enough there is an action potential and muscle contraction true/false
true
how do you get muscle weakness/paralysis from drugs
drugs effect end plate potential stopping it from reaching the threshold to open the ACh nicotinic receptors to produce an action potential
what is acetylcholinesterase
an enzyme which hydrolysis ACh therefor terminates its action
what is neuromyotomia
disease where the function of voltage activated potassium channels in the motor neurone axon and terminal doesn’t work
skeletal muscle fibres are over stimulated
symptoms of neuromyotmia
cramps
stiffness
slow relaxation (myotonia)
muscle twitches (fasciculation’s)
how do you treat neruomytomia
anti-epileptic drugs which block voltage activated sodium channels
what is Lambert Eaton Myasthenic syndrome
characterised by muscle weakness in limbs and associated with small cell carcinoma in the lungs
autoimmune origin
not enough ACh in the cleft
treatment for Lambert-eaton syndrome
anti cholinesterase - increases the concentration of ACh in the cleft by blocking enzyme which gets rid of it
What is myasthenia gravis
progressively increasing muscle weakness during periods of activity
often weakness of eye and eyelid
autoimmune
what is the mechanism of myasthenia gravis
antibodies against nicotinic ACh receptors in the end plate result in a reduction in the number of functional channels and hence the amplitude to the end plate potential
drug treatment for myasthenia gravis
anticholinesterases which increase the concentration of ACh in the synaptic cleft
what is botulinum toxin
extremely potent toxin that irreversibly inhibits Ach release
how can botulinum toxin be used clinically
low dose botulinum can be administered to treat overactive muscles
