treatment of MG inclused cholinesterase inhibitors
- pyridostigmine
- Edrophonium
- Summarise the mechanism of action potential (AP) generation and conduction in nerve and striated muscle.
An action potential arises as local potentials summate to push the membrane potential over the threshold at the axon hillock. The increased membrane potential trigger voltage gated sodium channels which trigger a massive influx of sodium into the cell which then make the inner cell massively positive. This polarisation inversion then triggers other sodium channels to open leading to a wave of depolarisations spreading down the muscle
- Neuromuscular junction – review the steps from arrival of AP to exocytosis.
ap arrive which makes voltage gated calcium channel open, triggering calcium to go into the cell and trigger vesicle release
- Neuromuscular junction- review steps from exocytosis to generation of AP. How is ACh removed from the cleft? Why are edrophonium and pyridostigmine useful in this case?
exocytosis of a excitatory Neurotransmitter causes chemical gated sodium channels to open, leading to a local positive charge inside the cell. With summation, either mechanical or freqeucy based, the membrane at the axon will depolarise. the Ach in the synaptic cleft is cleaved by acetylcholinesterase which prevents continuous sodium influx from a single presynaptic AP
- Summarise the mechanism of excitation - contraction coupling in skeletal muscle. How is contraction terminated?
the ap which passes along the sarcolemma of the muscle ends up interacting with the Dihydropyridine receptor which touches the Ryanodine receptor leading to the release of calcium ions into the myofibrils where they interact with troponin, tropomyosin leading to the bareing of attachment points for the myosin heads. the contraction is terminated by the calcium getting pumped back into the sarcoplasmic reticulum
- Where else outside the CNS is ACh used as a neurotransmitter? What is the autonomic nervous system and what types of ACh receptors types does it have? Account for the GI side effects of treatment.
The parasympathetic nervous system uses ACh as its primary neurotransmitter, treating for MG involves cholinesterase inhibitors, acting as a way to massively increase the functional ACh delivery with each ap. this has the unintended side effect of massively amplifying the functioning of the parasympathetic nervous system, which can lead to heart failure due to the inhibitory effects of the PS system onto the heart. Additionally GI will be dysregulated because of the amplified parasympathetic system. Atrophine inhibits muscinaric ACh receptors and will act as a inhibitory to the PS system to partially counter the effects of the pyridostigmine.
- What’s the problem in Myaesthenia gravis and how does it arise? Explain the abnormal EMG test result.
Myaesthenia gravis is characterised by a chronic immune reaction to the neuromuscular junction. this leads to fewer and fewer working junctions which end up leading to muscle weakness, as there is reduced nervous stimulation
- Briefly compare and contrast mechanisms of muscle weakness for botulinum toxin (including both systemic poisoning and local injection), tetanus toxin, curare, paralysis following local anaesthetic nerve block.
- botulinum toxin, blocking release of the ACh vesicles
- tetanus toxin inhibiting release of inhibitory neurotransmitters, leading to tetanus “duh”
- curare ACh antagonist
- local anesthetic nerve block stop signals from getting down an axon