Peter's Physiology Flashcards
Skeletal muscle is innervated by what type of neurones?
Alpha-motor neurones
Where are the cell bodies of alpha-motor neurones found? (2)
Spinal cord
Brainstem
The whole of the alpha-motor neurone is myelinated. T/F
False
Axons are initially myelinated but then become unmyelinated when they branch to supply individual muscle fibres
What is a motor unit?
The alpha-motor neurone and all of the skeletal muscle fibres that it innervates
Describe the structure of the axon branch which branches from a motor neurone axon to supply a single muscle fibre
- Unmyelinated
- Divides into multiple fine branches that end in a terminal bouton
Describe the structure of the axon branch which branches from a motor neurone axon to supply a single muscle fibre
- Unmyelinated
- Divides into multiple fine branches that end in a terminal bouton
What is the function of the terminal bouton of motor neurones? (2)
- Forms a chemical synapse with the muscle membrane at the neuromuscular junction
- AP’s in the cell body are conducted to cause ACh release
Describe the structure of the skeletal NMJ, making reference to the…
- Terminal bouton
- Synaptic vesicles
- Synaptic cleft
- The end plate region on the muscle cell membrane
- Nicotinic ACh receptors (nAChRs)
- Terminal bouton sits in close apposition with the muscle cell membrane
- Synaptic vesicles containing ACh line up in active zones inside the terminal bouton and await release when an AP arises
- Synaptic cleft is the space between the terminal bouton and the end plate region of the muscle cell membrane that ACh will cross
- The end plate region of the muscle cell membrane is thrown into a series of junctional folds
- nAChRs are found in regions of the junctional folds that face the active zones
Outline the synthesis, storage and exocytotic release of ACh
- ACh is synthesised from choline and acetyl CoA (by choline acetyltransferase) in the cytoplasm of the terminal bouton
- ACh is taken up into synaptic vesicles by the vesicular ACh transporter for concentration and storage
- ACh is released into the synaptic cleft by Ca2+-dependent exocytosis when an AP opens voltage-gated Ca2+ channels
What happens to ACh once it is exocytosed? (2)
- Briefly activates nicotinic ACh receptors (nAChRs) on the end plate region by reversibly binding to them
- Action rapidly terminated by acetylcholinesterase (AChE), which breaks ACh down in the synaptic cleft
Describe the structure of nicotinic ACh receptors (nAChRs)
- Made of 5 glycoprotein subunits
- Have 2 ACh binding sites
- Central cation selective pore allows for Na+ influx and K+ efflux when ACh binds
How does activation of nAChRs cause a depolarising (+ve) end plate potential (e.p.p.)?
Na+ influx is greater than K+ efflux
What is meant by the ‘quantum nature’ of ACh release?
- Each vesicle of ACh contains a ‘quantum’ of neurotransmitter that can cause a miniature end plate potential (m.e.p.p.)
- The e.p.p. is the summation of many m.e.p.p.’s due to many vesicles being released
How does e.p.p. initiate an AP in the muscle cell?
If the e.p.p. generated by the summation of the m.e.p.p.’s is sufficient to cross the threshold for opening of voltage-gated Na+ channels (+50mV), an AP is produced
Why is the muscle action potential required for muscle contraction, not just the e.p.p.?
- nAChRs at the muscle cell membrane mediate the e.p.p., which will wane as it spreads away from the endplate
- Voltage-gated Na+ channels will open along the muscle membrane and so can maintain the upstroke of the AP along the length of the muscle fibre
How does the muscle AP cause contraction?
AP arrival at T-tubules in the sarcoplasmic reticulum results in Ca2+ release from the SR lateral sacs
Ca2+ interacts with troponin to allow the actin-myosin cross-bridge to form
Why is there a delay between muscle AP and peak muscle contraction?
Time is required for Ca2+ to be released from the SR and cause cross-bridge formation
Why does a long relaxation period occur following muscle contraction?
Time is required for Ca2+ to unbind from troponin and be reabsorbed into the SR
Describe how acetylcholinesterase (AChE) terminates the action of ACh
AChE rapidly hydrolyses ACh into choline and acetate (sometimes even before it can bind to nAChRs)
What is the fate of choline and acetate in the synaptic cleft?
Choline is taken up by the sodium-choline transporter on the pre-synaptic neurone
Acetate diffuses from the synaptic cleft as an inactive metabolic byproduct
How do anti-cholinesterases work?
These are therapeutics that reversibly block the action of AChE to allow more ACh to be active in the synaptic cleft
List 3 clinical conditions in which transmission at the NMJ is defective
- Neuromyotonia
- Lambert-Eaton-Myasthenic Syndrome (LEMS)
- Myasthenia Gravis (MG)
List 2 medical treatments that interfere with transmission at the NMJ
- Botulism
- ‘Curare-like’ compounds
What is myasthenia gravis and how does it arise?
- An autoimmune disease with progressive worsening of muscle weakness with activity
- Arises as auto-antibodies target nAChRs and so they are reduced in number, resulting in a lower e.p.p. and less AP generation
What is neuromyotonia and how does it arise?
- An autoimmune disease with hyperexcitability of motor neurones and repetitive firing to skeletal muscle fibres
- Arises as auto-antibodies target voltage-gated K+ channels in the motor neurone
What is Lambert-Eaton Myasthenic Syndrome (LEMS) and how does it arise?
- An autoimmune disease associated with small cell lung cancer and characterised by muscle weakness in the limbs
- Arises as auto-antibodies target voltage-activated Ca2+ channels, reducing Ca2+ entry into the motor neurone and therefore ACh release is also reduced
How does the botulinum toxin act on the body?
It acts at motor neurone terminals to irreversibly inhibit ACh release, causing muscle paralysis
How do ‘curare-like’ compounds act in the body?
They act as competitive antagonists of the nAChRs which reduces the e.p.p. to below the threshold for muscle AP generation
When are botulinum toxins and ‘curare-like’ compounds used clinically?
Low dose botulinum toxins: to treat over-active muscles (e.g., eyelids) or to smooth out wrinkles
Curare-like compounds: used in surgery to produce reversible paralysis
