Physiology and Pharmacology of the Skeletal Neuromuscular Junction Flashcards
Professor John Peters
name the three types of muscle found in the body
cardiac
smooth
skeletal
what is skeletal muscle innervated by?
motor neurones
with myelinated axons and cell bodies in the spinal cord/brain stem
the neurone and the number of fibres that it innervates are know as what?
the motor unit
what chemical transmitter is found in skeletal muscle?
acetylcholine (ACh)
presynaptic terminal (bouton) of the alpha motor neurone synapses at what region of skeletal muscle fibres?
endplate
name the 4 key features of the skeletal neuromuscular junction
- terminal bouton with Schwann cells
- synaptic vesicles
- synaptic cleft
- end plate region
what are seen at active zones?
vesicles containing ACh
what receptor does ACh act on?
Nicotinic ACh receptor
what channels are concerned in he pre-synaptic process?
voltage-gated Ca2+ channels
what receptors does ACh activate?
nicotinic ACh receptors
when ACh is absent, is the gate open or closed?
closed
when does the receptor open?
when 2 molecules of ACh bond
Na+ efflux and K+ influx
true or false?
false
Na+ influx and K+ efflux
what is greater:
influx of Na+ or efflux of K+?
influx of Na+
net result is depolarisation known as end plate potential is generated
where is ACh stored and concentrated?
vesicles
what is one vesicle worth ACh known as?
a quantum
what is the electrical response to one quantum of transmitter known as?
miniature endplate potential
multiple m.e.p.p summates to the end plate potential
is the e.p.p. is large enough, what does it trigger the opening of?
voltage-activated Na+ channels - all or nothing response
where does the action potential enter in muscle?
transverse (T) tubules
releases Ca2+ which interacts with troponin causing contraction
what are the symptoms of neuromyotonia/NMT/Isaac’s syndrome?
muscle cramps, stiffness and twitches
what is the cause of neuromyotonia/NMT/Isaac’s syndrome?
autoimmune origin - antibodies against voltage gated K+ channels
what is the drug treatment in neuromyotonia/NMT/Isaac’s syndrome?
carbamazepine and phenytoin
what are the symptoms in Lambert-Eaton Myasthenic Syndrome (LEMS)?
muscle weakness - rare
what is Lambert-Eaton Myasthenic Syndrome (LEMS)
associated with?
small cell carcinoma of the lung
what is the cause of Lambert-Eaton Myasthenic Syndrome (LEMS)?
autoimmune origin - antibodies against voltage gated Ca2+ channels so reduced release of ACh
what is the drug treatment in Lambert-Eaton Myasthenic Syndrome (LEMS)?
anticholinesterases - pyridostigmine
potassium channel blockers - 3,4-diaminopyridine
what are the symptoms of Myasthenia Gravis (MG)?
progressively increasing muscle weakness during activity - eye and eyelid muscle
what is the cause of Myasthenia Gravis (MG)?
autoimmune origin - antibodies against nicotinic ACh receptors
what is the drug treatment in Myasthenia Gravis (MG)?
anticholinesterases - edrophonium for diagnosis, pyridostigmine for long term treatment
immunosuppressant agents - azathioprine
what is the botulinum toxin related to?
tetanus
what is the other name for botulinum toxin?
botox
what drugs Reduce the amplitude of the endplate potential (e.p.p.) to below the threshold for muscle fibre action potential generation?
curare-like compounds - competitive antagonists of nicotinic ACh receptors
vecuronium and atracurium
alpha-motor neurone and all the skeletal muscle fibres that it innervates is the…
motor unit
The action of ACh is terminated its hydrolysis of what?
acetylcholinesterase (AChE)
Botulism is caused by botulinum toxic which causes…
failure of ACh release - paralysis
