What triggers the fusion of synaptic vesicles with the pre-synaptic membrane?
An increase in cytosolic Ca2+.
What happens when ACh is released into the neuromuscular junction?
ACh binds to and opens nicotinic ACh receptor channels on the muscle fiber membranes (Na+, K+, Ca2+).
p.14
Excitation-Contraction Coupling
Which structures are involved in the process of excitation-contraction coupling?
Sarcoplasmic reticulum, calcium pump, actin filaments, and myosin filaments.
Where are ACh-gated channels located in the subneural clefts?
At the tops of the subneural clefts.
p.17
Excitation-Contraction Coupling
What happens to calcium after muscle contraction?
Calcium is pumped back into the SR and binds to calsequestrin to facilitate storage.
Where is acetylcholine (ACh) formed?
Acetylcholine (ACh) is formed in the cytoplasm.
p.9
Drug Effects on End Plate Potential
Why do ACh-like drugs have a prolonged effect?
Because they are not destroyed by AChE.
p.20
Malignant Hyperthermia
What causes the constant leak of SR Ca2+ in Malignant Hyperthermia?
Through the ryanodine receptor.
p.21
Skeletal Muscle Cramps
How does the build up of lactic acid in muscles trigger cramps?
The build up of lactic acid can cause muscle fatigue and discomfort, leading to cramps.
p.15
Excitation-Contraction Coupling
What is the role of the dihydropyridine receptor in the triad?
It acts as a voltage sensor.
Why does depolarization not occur in Myasthenia Gravis?
Due to weak end plate potentials.
Where are Ca2+ channels localized on the presynaptic membrane?
Around linear structures called dense bars.
p.14
Excitation-Contraction Coupling
What is the role of the calcium pump in excitation-contraction coupling?
Re-uptake of calcium ions.
p.1
Neuromuscular Junction
Where does the neuromuscular junction occur on the muscle fiber?
At a structure called the motor end plate.
p.13
Excitation-Contraction Coupling
What is the function of T-tubules in muscle fibers?
They penetrate the muscle fiber, branch, and form networks from one side to the other, transmitting action potentials deep into the muscle fiber.
p.17
Excitation-Contraction Coupling
What happens after the DHP receptor senses the voltage change?
The voltage change is communicated to the ryanodine receptor, which opens.
p.17
Excitation-Contraction Coupling
What marks the termination of muscle contraction?
Calcium is pumped back into the SR, and contraction is terminated.
What happens when ACh-filled vesicles fuse with the presynaptic membrane?
They release their contents, causing miniature end plate potentials (MEPP) in the postsynaptic membrane.
p.9
Drug Effects on End Plate Potential
What happens with each successive nerve impulse when Anti-AChE drugs are present?
Additional acetylcholine accumulates and stimulates muscle fiber repetitively.
p.20
Malignant Hyperthermia
Why is so much heat generated in Malignant Hyperthermia?
Our bodies are only about 45% energy efficient, with 55% of the energy appearing as heat.
p.10
Drug Effects on End Plate Potential
What are the treatments for Sarin poisoning?
The treatments are atropine and pralidoxime.
p.12
Lambert-Eaton Myasthenic Syndrome
How does anti-AChE (neostigmine) help in treating LEMS?
It increases the amount of ACh in the neuromuscular junction.
p.15
Excitation-Contraction Coupling
Where is the terminal cisternae located in the triad?
On either side of the T-tubule.
What is plasmapheresis and how is it used in Myasthenia Gravis treatment?
Plasmapheresis is the removal of antibodies and is used to treat Myasthenia Gravis.
What happens when local depolarization occurs in the motoneuron?
It opens voltage-gated Ca2+ channels.
p.1
Neuromuscular Junction
What components are labeled in the image of the neuromuscular junction?
Axon, sheath, terminal nerve branches, teloglial cell, myofibrils, muscle nuclei.
What enzyme is found in large quantities in the synaptic cleft?
Acetylcholinesterase (AChE).
p.13
Excitation-Contraction Coupling
What are the components of the sarcoplasmic reticulum?
Terminal cisternae and longitudinal tubules.
How are synaptic vesicles transported to the nerve terminal?
They are transported by axoplasmic streaming.
p.9
Drug Effects on End Plate Potential
What effect do ACh-like drugs have on muscle fibers?
They have the same effect on muscle fibers as ACh.
p.12
Lambert-Eaton Myasthenic Syndrome
What is the effect of LEMS on end plate potentials?
LEMS results in weak end plate potentials.
p.15
Excitation-Contraction Coupling
What is the 'Triad' in EC Coupling?
The junction between two terminal cisternae and a T-tubule.
What causes Myasthenia Gravis?
It is an autoimmune disease characterized by the presence of antibodies against the nicotinic ACh receptor, which damages or destroys them.
Where are voltage-gated Na+ channels located in the subneural cleft?
In the bottom half of the subneural cleft.
p.13
Excitation-Contraction Coupling
What are T-tubules?
Invaginations of the sarcolemma filled with extracellular fluid.
p.13
Excitation-Contraction Coupling
What is the role of terminal cisternae in the sarcoplasmic reticulum?
They form junctional 'feet' adjacent to the T-tubule membrane and serve as an intracellular storage compartment for Ca2+.
p.8
Drug Effects on End Plate Potential
What happens to the end plate potential when curare is present?
The end plate potential is weakened and too weak to generate an action potential.
How is acetylcholine (ACh) transported into the vesicles?
Acetylcholine (ACh) is transported into the vesicles from the cytoplasm.
p.9
Drug Effects on End Plate Potential
What are some examples of Anti-AChE drugs?
Neostigmine, physostigmine, diisopropyl fluorophosphate (nerve gas).
p.20
Malignant Hyperthermia
What are the symptoms of Malignant Hyperthermia?
Increased body temperature, skeletal muscle rigidity, and lactic acidosis (hypermetabolism).
p.10
Drug Effects on End Plate Potential
What is the cause of death from Sarin exposure?
Death occurs by asphyxia.
p.10
Drug Effects on End Plate Potential
How does atropine help in treating Sarin poisoning?
Atropine blocks muscarinic acetylcholine receptors, stopping seizures and convulsions.
p.15
Excitation-Contraction Coupling
What is the function of the ryanodine receptor in the triad?
It serves as a Ca2+ release channel.
How is Myasthenia Gravis usually treated?
It is usually ameliorated by anti-AChE (neostigmine), which increases the amount of ACh in the neuromuscular junction.
Approximately how many synaptic vesicles fuse with the pre-synaptic membrane during ACh release?
Approximately 125 synaptic vesicles.
p.1
Neuromuscular Junction
What is a neuromuscular junction?
A specialized synapse between a motoneuron and a muscle fiber.
Where are voltage-gated Na+ channels located in the subneural clefts?
In the bottom half of the subneural clefts.
p.8
Drug Effects on End Plate Potential
What is the effect of curariform drugs on the end plate potential?
They reduce the amplitude of the end plate potential, preventing an action potential.
Approximately how many acetylcholine (ACh) molecules are there per vesicle?
Approximately 10,000 per vesicle.
p.9
Drug Effects on End Plate Potential
How do Anti-AChE drugs affect acetylcholine degradation?
They block the degradation of ACh by inactivating acetylcholinesterase in the synapse.
p.10
Drug Effects on End Plate Potential
What is Sarin?
Sarin is a nerve gas and a potent inhibitor of acetylcholinesterase, which raises acetylcholine levels.
p.12
Lambert-Eaton Myasthenic Syndrome
What are the primary symptoms of Lambert-Eaton Myasthenic Syndrome?
Muscle weakness and paralysis.
p.12
Lambert-Eaton Myasthenic Syndrome
What treatments are available for Lambert-Eaton Myasthenic Syndrome?
Anti-AChE (neostigmine), chemotherapy with radiation therapy, and plasmapheresis (less effective).
p.15
Excitation-Contraction Coupling
What structures form the triad in muscle cells?
Two terminal cisternae of the sarcoplasmic reticulum (SR) and a T-tubule.
What drugs are used to suppress the immune system in Myasthenia Gravis treatment?
Prednisone and other drugs.
Where does the action potential (AP) begin in the process of ACh release?
In the ventral horn of the spinal cord.
What type of channel is the acetylcholine-gated channel?
It is a cation channel that does not differentiate between sodium, potassium, and calcium.
p.7
End Plate Potential and Action Potential
What can an end plate potential initiate if the local spread of current is sufficient?
An action potential (AP).
p.1
Neuromuscular Junction
How many motor end plates are usually present per muscle fiber?
Usually only one per fiber.
What is the synaptic trough?
An invagination in the motor end plate membrane.
p.2
Neuromuscular Junction
What is the neuromuscular junction?
The junction between a single axon terminal and muscle fiber membrane.
p.13
Excitation-Contraction Coupling
Where does each T-tubule lie in relation to the sarcoplasmic reticulum?
Each T-tubule lies adjacent to the ends of longitudinal sarcoplasmic reticulum tubules that surround all sides of the actual myofibrils that contract.
Do miniature end plate potentials (MEPP) cause muscle contraction?
No, MEPPs do not cause contraction.
p.9
Drug Effects on End Plate Potential
What is the overall effect of Anti-AChE drugs on acetylcholine?
They prolong the effect of acetylcholine.
p.10
Drug Effects on End Plate Potential
How much more deadly is Sarin compared to cyanide?
Sarin is 26 times more deadly than cyanide.
p.12
Lambert-Eaton Myasthenic Syndrome
What causes Lambert-Eaton Myasthenic Syndrome?
An autoimmune attack against voltage-gated calcium channels on the presynaptic motor nerve terminal.
p.21
Skeletal Muscle Cramps
What is the precise cause of nocturnal leg muscle cramps?
The precise cause is unknown.
What is the incidence rate of Myasthenia Gravis according to www.gpnotebook.co.uk?
10-15 per 100,000 people per year.
Where are acetylcholine receptors located in the subneural cleft?
At the top of the subneural cleft.
What happens when acetylcholine attaches to its binding site on the channel?
A conformational change opens the channel, allowing sodium to enter the muscle fiber and excite contraction.
p.14
Excitation-Contraction Coupling
What happens to calcium ions after they are released from the sarcoplasmic reticulum?
They are re-uptaken by the calcium pump.
What is the function of subneural clefts?
They increase the surface area of the postsynaptic membrane.
p.8
Drug Effects on End Plate Potential
How do curariform drugs (D-tubocurarine) affect nicotinic ACh channels?
They block nicotinic ACh channels by competing for the ACh binding site.
p.8
Drug Effects on End Plate Potential
What is the consequence of botulinum toxin decreasing ACh release?
There is an insufficient stimulus to initiate an action potential.
Approximately how many synaptic vesicles are there per terminal?
Approximately 300,000 per terminal.
p.9
Drug Effects on End Plate Potential
How do ACh-like drugs interact with nicotinic ACh receptors?
They bind and activate nicotinic ACh receptors.
p.20
Malignant Hyperthermia
What triggers Malignant Hyperthermia?
Halogenated anesthetics such as isoflurane and halothane.
p.10
Drug Effects on End Plate Potential
How does Sarin inhibit acetylcholinesterase?
Sarin forms a covalent bond with serine at a particular site on acetylcholinesterase, with fluoride as the leaving group.
p.10
Drug Effects on End Plate Potential
How does pralidoxime work in treating Sarin poisoning?
Pralidoxime binds to organophosphate-inactivated acetylcholinesterase, causing its release and reactivating acetylcholinesterase.
p.21
Skeletal Muscle Cramps
How can dehydration contribute to nocturnal leg muscle cramps?
Dehydration can lead to an imbalance of electrolytes, which may trigger muscle cramps.
What are the symptoms of Myasthenia Gravis?
Paralysis, which can be lethal in extreme cases when respiratory muscles are involved.
What happens to vesicles filled with acetylcholine at the release site?
They fuse with the membrane in the region of the dense bars and release acetylcholine to the synaptic space via exocytosis.
What is the net inward movement of positive ions through the acetylcholine-gated channel?
Mostly Na+ (sodium), but also some Ca++ (calcium).
p.8
Drug Effects on End Plate Potential
How does botulinum toxin affect ACh release?
It decreases the release of ACh from nerve terminals.
Where are synaptic vesicles formed?
Synaptic vesicles are formed from budding Golgi.
p.9
Drug Effects on End Plate Potential
What are some examples of ACh-like drugs?
Methacholine, carbachol, nicotine.
p.16
Excitation-Contraction Coupling
What role does calsequestrin play in muscle cells?
It binds calcium within the sarcoplasmic reticulum.
p.21
Skeletal Muscle Cramps
What are some possible contributing factors to nocturnal leg muscle cramps?
Dehydration, low levels of Mg++, K+, Ca++, and Na+, and build up of lactic acid in muscles.
What is the incidence rate of Myasthenia Gravis according to www.emedicine.com?
2 per 1,000,000 people per year.
p.18
Excitation-Contraction Coupling
What initiates the sequence of events in EC coupling in cardiac muscle?
An action potential (AP) moves along the T-tubule.
p.18
Excitation-Contraction Coupling
How is calcium removed from the cytoplasm to terminate contraction in cardiac muscle?
Calcium is pumped back into the sarcoplasmic reticulum (SR) and back into the T-tubule.
p.18
Excitation-Contraction Coupling
What is the role of the Ca2+/Na+ exchanger in cardiac muscle?
The Ca2+/Na+ exchanger removes Ca2+ from the cell by exchanging it with Na+.
p.18
Excitation-Contraction Coupling
What is required for the Ca2+ pump to function in cardiac muscle?
ATP is required for the Ca2+ pump to function.
p.18
Excitation-Contraction Coupling
What role do DHP receptors play in EC coupling in cardiac muscle?
DHP receptors act as voltage sensors that release a small amount of Ca into the fiber.
p.18
Excitation-Contraction Coupling
What happens after Ca is released by DHP receptors in cardiac muscle?
Ca binds to the ryanodine receptor, which opens and releases a large amount of Ca (CACR).
p.18
Excitation-Contraction Coupling
What is the function of calsequestrin in cardiac muscle?
Calsequestrin helps in storing calcium within the sarcoplasmic reticulum.
