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29 Cards in this Set
- Front
- Back
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What is the most prevalent disease that affects synaptic transmission? |
Myasthenia gravis |
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What is myasthenia gravis?
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A disorder of function at the synapse between cholinergic motor neurons and skeletal muscle
An autoimmune disorder in which antibodies are produced against the nicotinic acetylcholine receptor |
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What do the antibodies produced do? |
Interfere with synaptic transmission by reducing the number of functional receptors or by impeding the interaction of ACh with its receptors |
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What are four special characteristics of the weakness in myasthenia gravis?
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1) Cranial muscles as well as limb muscles
2) Varies within the course of a single day, from day to day, or over longer periods (remission and exacerbation) 3) No conventional clinical signs, no electromyographic signs of denervation 4) Reversed by drugs that inhibit acetylcholinesterase |
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How does the brain look at autopsy? |
CNS and PNS look normal, so disorder of function |
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Describe the amplitude of evoked compound action potentials in MG. |
Decreases rapidly like when curare is applied |
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What do 15% of adult patients with MG have and what does it imply? |
A benign tumor of the thymus Suggests MG is an immunological disorder |
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What toxin would you use to isolate ACh receptors? |
alpha-bungarotoxin |
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How would you determine how many binding sites on receptors are open? |
Radiolabeled alpha-bungarotoxin |
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What are the essential characteristics of MG? |
1) Reduction in amplitude of the miniature end-plate potentials 2) Smoothing of the normal convoluted appearance of the postjunctional folds 3) A loss of ACh receptors from the crests of junctional folds 4) Deposition at junctional sites of antibody and complement |
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What is plasmapheresis? |
A procedure in which blood is removed from a patient, cells are separated from plasma, and the cells alone returned to the patient; relieves MG patients of symptoms |
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What causes the characteristic decrease in the response of MG muscle to repetitive stimulation? |
Increased diffusion of ACh due to lack of folds, amplitude reduced past the safety factor |
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What is the safety factor? |
In normal muscle, the difference between the threshold and the actual end-plate potential is large |
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What is jitter? |
The normal variation in intervals between discharges of different muscle fibers innervated by the same motor neuron |
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To which sites on the ACh receptor do the antibodies in MG bind? |
The bungarotoxin-binding site An area on the alpha subunit called the main immunogenic region |
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What initiates the production of antibodies to the ACh receptor? |
Could be a viral infection that shares epitopes with the receptor |
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How do antibodies cause symptoms? |
Don't occupy the receptor site Trigger the receptor's internalization |
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What three molecules does the autoimmune response depend on?
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1) The antigen: ACh receptor
2) An antigen-specific T cell receptor 3) Class II molecules of the major histocompatibility complex (MHC) that are expressed on the antigen-presenting cell |
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How might you cure MG? |
Antibodies against the antibodies Develop peptide competitors for ACh receptors that might block T-cell recognition of ACh receptors |
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Is MG one syndrome or is it heterogeneous? |
Heteregeneous |
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What happens with a lack of acetylcholinesterase? |
Decrease in response to repetitive stimulation EPPs aren't small, but are prolonged ACh receptors are preserved |
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What are two other disorders part of the MG syndrome? |
Congenital lack of acetylcholinesterase Slow-channel syndrome |
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Describe the slow-channel syndrome. |
Limb weakness, little cranial muscle weakness EPPs are prolonged Opening of ACh receptor-channel is abnormally long Miniature EPPs are abnormally low amplitude Possible that the developmental transition from slow to fast channels is prevented Could be a mutation of the ACh receptor |
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What is facilitating neuromuscular block? |
The opposite of MG A gradual increase in response |
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What is Lambert-Eaton syndrome? |
Facilitating neuromuscular block Presence of antibodies to voltage-gated Ca2+ channels Loss of the active zones |
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How can you improve Lambert-Eaton syndrome? |
Plasmapheresis or immunosuppressive drugs |
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What does botulism do at the NMJ? |
Impaired release of ACh |
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How would you treat Lambert-Eaton and botulism? |
Agents that promote the release of ACh |
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What is the strategy to treat diseases of synaptic function? |
1) Determine whether the origin is in the presynaptic neuron or the postsynaptic neuron 2) Correct the affected step in transmission or eliminate the pathogenic agent |
