Electrophysiology BSC Flashcards
Symptoms: enlarged thymus gland, difficulty reading occuring more often in evenings, combination of diplopia(double vision) and blurred vision. normal neurological sensory responses. DTR’s normal, but small degree of muscle weakness deteceted. Vision problems du to extraoculuar muscle weakness. Ab’s against nAChR present in plasma…….
Diagnosis = myasthenia gravis
—> weakness and fatigue (worsens with increased activty, improves with rest)
Muscular symptoms: usually extraoculuar mm. initiatially affected (ptosis=drooping of eyelid, blurred vision). bulbar muscles (speech and swallowing), neck muscles and proximal limb muscles also affected
- neural conduction, sensory and autonomic responses are normal
- circulating Abss directed against nAChR commonly detected
What does the effect of normal presynaptic release of ACh have on the motor end plate with people with Myasthenia Gravis? Why?
- the end plate potential would likely be decreased, but not absent, because they still have some nAChR, but just a decreased amount.
- they have a decreased amount of nACh receptors because anti-nicotinic ACh Ab’s are produced which bind and block the receptor binding of ACh
- thus fewer channels are capable of opening in response to ACh, resulting in a decreased ability to generate an end-plate potential.
What is the specific mechanism by which ACh release resutls in an endplate potential (EPP)? What is the normal effect of an EPP on the sarcolemma of a skeletal muscle fiber?
- ACh binds the nicotinic AChR, resulting in the opening of the ACHR channel at the motor plate, resulting in an EPP
- this results in an influx of cations Na+ and K+, resulting in raising the Vm toward threshold
* Vm shifts to a value between EK (−80 mV) and ENa (+50 mV) - threshold is reached on adjacent sarcolemma, voltage gated Na+ channels open, and a muscle AP is generated
Why do some patients with ptosis show temporary improvement with an Ice Pack Test?
b/c the cooling slows down or inhibits AChE activity - thus there is more ACh left in the cleft, and more likely to bind to the nAChR that are still operating.
Presentation: proximal weakness and absent tendon reflexes. EMG initially shows low-amplitude muscle response which significantly increases following repeated activation. Circulating Ab’s directed against voltage-gated CA2+ channels are detected…..
Diagnosis: Lambert-Eaton Myasthenic Syndrome (LEMS)
- Paraneoplastic syndrome
What is LEMS?
Autoimmune attack directed against voltage-gated calcium channels (VGCCs) on the presynaptic motor nerve terminal - results in a Loss of functional VGCCs
- synaptotagmin is the main Ca2+ sensor
Why does repetitive stimulation result in increased contractile strength in our patient with Lambert-Eaton vs. decreased strength following repetitive use in our patient with Myasthenia gravis?
LEMS:
- Rapid repetitive stimulation can increase Ca2+ influx via functioning channels, increasing the release of ACh
- Presynaptic stores of ACh and postsynaptic AChR are intact the EPP will raise the membrane above threshold and permit generation of muscle AP
Symptoms: dry mouth, double vision, diff. swallowing/speaking, vomiting, diarrhea. stool tested positive for clostridium botulinum.
- Botulinum toxin, along with tetanus toxin act to limit the release of ACh
what are the effects of tetanus and botulinum?
- prevent the docking and fusion of the synaptic vesicle
tetanus –> inhibits synaptobrevin
botulinum B,D,F,G –> synaptobrevin
botulinum A/E –> SNAP-25
botulinum C1–> syntaxin
Symptoms:
Severe weakness during period of rest after exercise
Weakness after eating bananas
Periodic muscle spasms and myotonia, weakness
Diagnosis: Hyperkalemic Periodic Parlysis
Often triggered by:
- Exercise, stress, fasting, or ingestion of large amounts of K+
- For unknown reasons, exercise-induced paralysis occurs after exercise, not during
- Autosomal dominant trait affecting the skeletal muscle gene SCN4A, located on chromosome 17 - Mutation impairs fast-inactivation of voltage-gated Na+ channels
What effect does hyperkalemia normally have on resting membrane potential?
↑ ECF K+ (hyperkalemia): ↓ K+ efflux (or promote K+ influx) - (membrane potential becomes less negative, depolarized, as the + charge remains in the cell)
What is the impact on membrane potential if some mutant Na+ channels do not inactivate properly?
- Small, persistent influx of Na+
- Continues to depolarize the membrane
- Membrane potential is closer to threshold → hyperexcitablilty
Fasciculations (spontaneous twitches), muscle spasms at rest, myotonia (stiffness)
- Additional prolonged depolarization, as is in this case with hyperkalemia, compounds the voltage-gated Na+ channelopathy
- Channels are effectively in an absolute refractory period - because the membrane potential is above resting, and is very positive
In addition to the initial depolarization caused by non-inactivating mutant Na+ channels,
- Hyperkalemia further contributes to membrane depolarization, and slows repolarization
- Wild-type Na+ channels are able to inactivate and remain inactivated (“closed and locked”) until repolarization (“re-set) occurs
Inactivation prevents AP initiation and results in paralysis observed
Why do people with hyperkalemic periodic paralysis show both fasciculations (spontaneous twitches),mkuslce twitches, myotonia(stiffness) and weakness or paralysis?
Mild depolarization (5-10 mV):
- May be caused by increased ECF [K+] and/or due to influx via mutant Na+ channels which do not inactivate
- Persistent Na+ influx → depolarization closer to threshold repetitive AP firing
- Myotonia (stiffness), hyperexcitability
Greater depolarization (20-30 mV):
- Normal, wild-type Na+ channels fix in inactivation state
- Do not reset until repolarization
- Weakness or paralysis
Subtle differences in degree of membrane depolarization can make the difference between myotonia and paralysis
why would carbohydrate/glucose intake help people with hyperkalemic periodic paralysis?
To reduce plasma K+ levels in attempt to alleviate the HyperPP attacks:
Insulin promotes transport of extracellular K+ into the cell by activating the Na+/K+ pump
High carbohydrate diet and glucose promote insulin secretion, facilitating a decrease ECF [K+]
Case: malignant hyperthermia, muscle rigidity, tachypnea, tachycardia experienced when under general anesthetic
Diagnosis: malignant hyperthermia: rare, heritable condition (autosomal dominant trait) that can be triggered by anesthesia and results in a potentially fatal increase in body temperature.
What is the effect?
Disorder of Ca2+ regulation in skeletal muscle triggered by volatile anesthetics & muscle relaxers
- Uncontrolled release of Ca2+ from the SR → rigidity, tachycardia, hyperventilation, and hyperthermia
- Acute hyper-metabolic state within muscle tissue; prolonged contraction
