8 - Action Potentials at Neuromuscular Junction Flashcards
What happens at the nerve terminal of a neuromuscular junction?
If a stimulus is stronger, e.g being hit instead of being tickled, how is this information relayed to the brain?
- Increase in frequency of action potentials
- More action potentials means more Ca2+ entry
- More neurotransmitter released
What is the structure of a voltage gated Ca channel?
- Very similar to Na, only needs one a subunit activated to be functional
- Activates and inactivates but much slower than Na channels
What are the different isoforms of Ca channels and where are they found?
How can L-type channels be utilised?
- Use DHP’s to block channels
- Blocks entry of Ca2+ into smooth muscle cells, e.g smooth muscle of artery
- Prevents contraction
- Treat hypertension
What is the subunit compositon of Ca and Na channels?
- Pore forming alpha subunit
- Other subunits associate with this and regulate the activity of the pore
How does an influx of Ca2+ in the cell promote neurotransmitter release?
What happens at the neuromuscular junction once ACh has been released?
What are neuromuscular blockers?
- Block AChR
How does d-tubocurarine work?
- Similar shape to ACh, binds to AChR, antagonist
- Blocks receptor as channel cannot open, can’t reach threshold for A.P
- Increase ACh can overcome blocking
How does succinylcholine work?
- Depolarising inhibitor
- Can activate AChR but cannot be degraded by AChE so continual depolarisation
- Adjacent Na channels will constantly be inactive so cannot open and stimulate new action potential
- Cannot overcome by increasing ACh
How can neuromuscular blockers be used?
- Can be used in conjuction with general anaesthetic for temporary paralysis, causing muscles to be relaxed for easier surgery
- Person paralysed with these blockers can appear to be under general anaesthesia but can still feel pain but unable to speak or move
What happens during myasthenia gravis?
- Autoimmune disease, antibodies against AChR so less AChR due to lysis and degradation
- Lowers amplitude of endplate potential so may not reach threshold
- Muscle weakness that is made worse by exercise
How do you diagnose and treat myasthenia gravis?
Edrophonium test
Promote facial weakness with repeated facial movements. Inject edrophonium chlorine (anticholinesterase) slowly IV and facial weakness will be relieved
Always needs to be done in hospital with resus facilities and syringe of atropine (muscarinic receptor antagonist)
How do insecticides kill you?
- Contain organophosphates
- Form irreversible covalent bond with AChE, inhibiting it
- Continual depolarisation
- Recovery takes few weeks as synthesis of new AChE needed
SLUDGE AND DUMBELS
What is the difference between nAChR and mAChR’s?
When does myelination occur?
3rd trimester of pregancy (28th week) and then rapid myelination up to age 2
What is hypertension?
Sustained elevation in resting blood pressure, over 140/90 mmHg
What is secondary hypertension?
Cause of hypertension known, e.g renal disease, pheochromocytoma
How is blood pressure raised naturally?
Increased cardiac output, baroreceptors detect and send a signal to the brain. This increase renal blood flow. Causes kidneys to release renin.
Renin causes angiotensinogen to be converted to angiotensin by ACE. This stimulates aldosterone release and causes vasoconstriction. Aldosterone then acts on kidney, increasing sodium retention, and therefore water retention so higher blood pressure
What drugs can be used to reduce blood volume?
- Diuretics
- ACE antagonists to prevent production of angiotensin II
What drugs can cause vasodilation?
- Alpha blockers
- Calcium channel blockers
Unwanted side effects of alpha 1 antagonists?
- diarrhoea
- impotence
- tachycardia
How do beta 1 antagonists lower blood pressure?
- Negative chronotropy and isotropy
- Prevent renin release
Why should you think about side effects for hypertension drugs?
Hypertension normally asymptomatic but side effects have symptoms so lowers compliance of patient. This can lead to lots of risks, risk of getting diabetes mellitus etc so need to have drug with low side effects
