Physiology: NMJ Flashcards
List and explain in sequence the steps involved in neuromuscular transmission in skeletal muscle and point out the location of each step on a diagram on NMJ.
- Action potential comes to the NMJ.
- Opening of voltage gated Ca2+ channel.
- Influx of Ca2+ causes binding of vesicles to presynaptic membrane and causes exocytosis, which is caused by synapsin 1.
- Ca2+ phosphoralates synapsin I and causes it (transmitter) to be removed from the vesicles. - Ach binds to receptor of the postsynaptic cell.
- Ach is broken down by acetylcholinesterase.
- Choline is transferred back into the axon terminal to make more ACh.
Discuss the 4 steps in which SNARE proteins are involved in transmitter release.
- Vesicle moves to the active zone.
- Several protein participate by attaching vesicle to active zone.
- SNARE proteins docks the vesicle to the membrane
- Fusion of vesicle and membrane required an increase in intracellular Ca2+. Ca2+ binds to synaptogamin, permitting fast fusion between the vesicle and membrane.
Explain the concepts of quantal release.
Quantal release is the amount of neurotransmitter contained within the vesicles. These are released due to the change in the membrane potential of a muscle cell.
Explain the concepts of receptor reserve.
A percentage of receptors that must be blocked before any effect on the muscle can take place.
Note:
A receptor must be occupied by 75% in order for a muscle contraction to take place.
Describe the location, structure and receptor subtypes of the acetylcholine receptor and their associated second messenger systems.
- Receptor - Nicotinic
- Location - post synaptic cell
- Structure - Rosette form
- Subtypes- 5 subunits. (2 alpha. 1 beta, 1 delta, 1 epsilon)
- Associated 2nd messenger systems - ACh or exogenous agonist. (Need for all or none opening)
List the possible sites for blocking neuromuscular transmission in the skeletal muscle.
Presynaptically - inhibit ACh synthesis and release
Postsynaptically - inhibiting ACh from binding to NM receptor.
Give an example of an agent that could cause neuromuscular transmission blockage at each site.
Non - Depolarizing - Tubocurarine
Depolarizing - Succinylcholine
Compare and contrast depolarizing blockade of the neuromuscular junction with non-depolarizing blockade.
- Non- Depolarizing blockade involves the blocking of the NM receptor. No depolarization. Competes with ACh to prevent EPP from being large enough to activate a muscle contraction.
- Depolarizing blockage involves acting as agonist at the NM receptor. Depolarizes skeletal muscle. Prolong can causes paralysis
List examples of common drugs used in neuromuscular blockade.
Non - Depolarizing - Curare.
Depolarizing - Succylncholine
Explain the depolarizing blockade.
- Agonists NM receptor
- Fasciculation and twitches seen on onset.
- Over use (prolong depolarization) can cause paralysis
- No more action potentials.
- Resistant to achytehcholinesterase.
Discuss the physiological principles involved in myasthenia gravis.
- Antibodies affect the ACh receptor by decreasing the amount of receptors on the end plate and reducing postsynaptic membrane folds.
Discuss the physiological principles involved in Eaton Lambert syndrome. (LEMS)
- Autoimmune disease that results in the non functioning of Ca2+ channels on the NMJ membrane.
- The non working channels prevents ACh from leaving the cells.
- Results in ACh not targeting muscles to contract this causing weakness.
Discuss the physiological principles involved in malignant hyperthermia.
- Triggered by anesthetics and neuromuscular agents.
- Caused by a defect in the ryanodine receptor.
- An uncontrolled amount of Ca2+ is released from the SR thus causing contracture and increase in body temperature.
Discuss the clinical presentation of myasthenia gravis.
- Fluctuating weakness
- Head flexion and exertion weakness
- Extra ocular muscle weakness
Discuss the role of Dantrolene in Malignant hyperthermia.
It blocks the inappropriate response of ryanodine receptor and prevents Ca2+ loss.
Decreases Ca2+ efflux from SR.
