L9: The Neuromuscular Junction Flashcards
What is the neuromuscular junction?
It is a specialized synapse between a motor neuron and a skeletal muscle fiber, ensuring reliable and rapid signal transmission.
What neurotransmitter is primarily involved in the neuromuscular junction?
Acetylcholine (ACh).
What structure increases the surface area of the postsynaptic membrane at the neuromuscular junction?
Junctional folds.
What enzyme terminates the signal at the neuromuscular junction?
Acetylcholinesterase.
What are the main ion movements during postsynaptic depolarization in the neuromuscular junction?
Sodium ions (Na⁺) enter the cell, and potassium ions (K⁺) leave.
What receptor type is found on the postsynaptic membrane of the neuromuscular junction?
Nicotinic acetylcholine receptors.
How is the action potential initiated at the neuromuscular junction propagated into the muscle fiber?
Through the T-tubule system.
What is the main role of the sarcoplasmic reticulum in muscle contraction?
To store and release calcium ions (Ca²⁺), which trigger muscle contraction.
What condition is characterized by fatigue and muscle weakness due to neuromuscular junction dysfunction?
Myasthenia Gravis.
How does Myasthenia Gravis impair neuromuscular transmission?
It involves antibodies attacking nicotinic acetylcholine receptors, reducing their number and function.
What type of drug is used to treat Myasthenia Gravis?
Acetylcholinesterase inhibitors, which prolong the presence of acetylcholine in the synaptic cleft.
What is an end-plate potential?
A large depolarization at the neuromuscular junction caused by acetylcholine receptor activation.
What ion is critical for neurotransmitter release at the presynaptic terminal?
Calcium ions (Ca²⁺).
What are the two electrical events at the neuromuscular junction?
The ligand-gated sodium influx causing depolarization, followed by action potential propagation via voltage-gated sodium channels.
How is calcium involved in presynaptic neurotransmitter release?
Voltage-gated calcium channels open, allowing calcium to enter and trigger vesicle fusion with the membrane.
What is the main function of the neuromuscular junction?
To reliably transmit signals from motor neurons to muscle fibers, resulting in muscle contraction.
Where are the cell bodies of motor neurons located?
In the ventral horn of the spinal cord.
What distinguishes the neuromuscular junction from synapses in the central nervous system?
It is highly specialized, with structural features like junctional folds and high densities of acetylcholine receptors to ensure reliable signal transmission.
What is the role of voltage-gated calcium channels in the presynaptic terminal?
They open in response to depolarization, allowing calcium ions to enter and trigger vesicle exocytosis.
What is the calcium sensor protein that initiates vesicle fusion during exocytosis?
Synaptotagmin.
How does acetylcholine cause depolarization in the postsynaptic muscle cell?
By binding to nicotinic receptors, opening ion channels that allow sodium influx and potassium efflux.
What is the effect of the large depolarization caused by acetylcholine at the neuromuscular junction?
It triggers an action potential that propagates across the muscle membrane.
What is the function of the T-tubule system in muscle fibers?
It transmits the action potential deep into the muscle to activate contraction mechanisms.
What is the DHP receptor, and what is its role in muscle contraction?
The DHP receptor (dihydropyridine receptor) is a voltage sensor that triggers calcium release from the sarcoplasmic reticulum.
What channel releases calcium from the sarcoplasmic reticulum into the muscle cytoplasm?
The ryanodine receptor.
Why is rapid acetylcholine breakdown important at the neuromuscular junction?
To ensure precise control of muscle contraction and prevent continuous stimulation.
How does myasthenia gravis affect eye muscles specifically?
Eye muscles are used frequently, making them more prone to fatigue in this condition.
What is temporal summation in the context of muscle contraction?
The increase in muscle contraction strength when stimuli are delivered in rapid succession.
How does the neuromuscular junction achieve reliable transmission?
Through high densities of acetylcholine receptors, abundant synaptic vesicles, and structural adaptations like junctional folds.
What happens if acetylcholinesterase is inhibited?
Acetylcholine remains in the synaptic cleft longer, enhancing receptor activation and muscle contraction.
What is the resting membrane potential of the neuromuscular junction, and how does it compare to central nervous system synapses?
It is approximately -90 mV, which is more negative than the typical -65 mV in central nervous system neurons.
What is the role of ligand-gated ion channels in the neuromuscular junction?
They mediate the initial depolarization by allowing sodium influx upon acetylcholine binding.
What is the significance of multiple vesicle release in the neuromuscular junction?
It ensures a large release of acetylcholine, resulting in a strong and reliable depolarization (end-plate potential).
What clinical symptom is most commonly associated with myasthenia gravis?
Muscle weakness, particularly in the eyes and eyelids, due to rapid fatigue of affected muscles.
What distinguishes the postsynaptic membrane at the neuromuscular junction?
It has junctional folds that increase the surface area for acetylcholine receptor expression, enhancing signal transmission efficiency.
What causes the release of neurotransmitters in the presynaptic terminal?
An influx of calcium ions (Ca²⁺) into the presynaptic terminal triggers vesicle fusion and neurotransmitter release.
What happens during exocytosis at the neuromuscular junction?
Vesicles containing acetylcholine fuse with the presynaptic membrane, releasing the neurotransmitter into the synaptic cleft.
What is the role of the sarcoplasmic reticulum in muscle contraction?
It stores calcium ions and releases them in response to signals, initiating muscle contraction.
What ensures that acetylcholine release reliably triggers muscle contraction?
The large number of acetylcholine-containing vesicles and the high density of postsynaptic receptors.
How is acetylcholine synthesized in the neuron?
From choline and acetyl-CoA, catalyzed by the enzyme choline acetyltransferase.
What is the fate of acetylcholine after it has bound to receptors?
It is broken down into acetate and choline by acetylcholinesterase, and choline is taken back up by the presynaptic neuron for reuse.
What is the difference between ligand-gated and voltage-gated ion channels at the neuromuscular junction?
Ligand-gated channels open in response to acetylcholine binding, while voltage-gated channels open in response to changes in membrane potential.
What is the equilibrium potential for sodium (Na⁺) at the neuromuscular junction?
Approximately +60 mV, which drives sodium into the cell during depolarization.
What is the equilibrium potential for potassium (K⁺) at the neuromuscular junction?
Approximately -90 mV, which means potassium has little initial driving force but increases as depolarization progresses.
Why does potassium eventually flow out of the cell during depolarization?
Depolarization moves the membrane potential away from potassium’s equilibrium potential, creating a driving force for its efflux.
What are the two main phases of electrical signaling at the neuromuscular junction?
The initial ligand-gated depolarization and the subsequent action potential propagation via voltage-gated sodium channels.
What is summation in the context of muscle contraction?
The additive effect of multiple rapid signals leading to sustained contraction rather than individual twitches.
What structural feature allows the action potential to invade the interior of the muscle fiber?
The T-tubule system (transverse tubules).
How does depolarization lead to calcium release from the sarcoplasmic reticulum?
The DHP receptor detects depolarization and triggers the ryanodine receptor to release calcium from the sarcoplasmic reticulum.
What condition results from the immune system attacking acetylcholine receptors at the neuromuscular junction?
Myasthenia Gravis.
Why is calcium critical for both neurotransmitter release and muscle contraction?
It triggers vesicle fusion for neurotransmitter release and activates contractile proteins in the muscle.
What is the typical duration of a synaptic event at the neuromuscular junction?
Approximately 1 millisecond.
What electrical event propagates along the muscle membrane after the initial depolarization?
An action potential.
How is the large depolarization at the neuromuscular junction termed?
End-plate potential (EPP).
What happens to calcium after muscle contraction is completed?
It is pumped back into the sarcoplasmic reticulum to terminate contraction and reset the system.
What is the main structural difference between the neuromuscular junction and central nervous system synapses?
The neuromuscular junction has junctional folds and a much higher density of acetylcholine receptors, while CNS synapses have fewer receptors and lack such folds.
How does acetylcholine binding affect nicotinic acetylcholine receptors?
It causes a conformational change that opens an ion channel, allowing sodium (Na⁺) to enter and potassium (K⁺) to exit the muscle cell.
What ensures the rapid onset of action potentials at the neuromuscular junction?
The high density of voltage-gated sodium channels near the end-plate potential ensures efficient propagation of the signal.
What are the primary forces driving sodium (Na⁺) influx during depolarization?
Sodium influx is driven by both a chemical gradient (higher Na⁺ concentration outside the cell) and an electrical gradient (negative resting membrane potential).
Why is there minimal potassium (K⁺) efflux at the start of depolarization?
The resting membrane potential is close to potassium’s equilibrium potential, resulting in a weak driving force for potassium efflux initially.
What happens to the postsynaptic membrane potential during an end-plate potential (EPP)?
The membrane potential depolarizes from approximately -90 mV towards the threshold for an action potential.
What proteins are involved in vesicle docking and fusion during neurotransmitter release?
SNARE proteins and synaptotagmin play key roles in the docking and fusion of vesicles with the presynaptic membrane.
What role does the DHP receptor play in excitation-contraction coupling?
It acts as a voltage sensor that triggers the ryanodine receptor to release calcium from the sarcoplasmic reticulum.
What is the function of the ryanodine receptor in muscle contraction?
It releases calcium ions from the sarcoplasmic reticulum in response to signals from the DHP receptor, initiating contraction.
How is acetylcholine synthesized and stored?
Acetylcholine is synthesized from choline and acetyl-CoA by choline acetyltransferase and stored in vesicles in the presynaptic terminal.
What is a quantum of neurotransmitter release?
A quantum refers to the release of acetylcholine from a single vesicle, typically containing around 4,000 molecules of acetylcholine.
Why is the neuromuscular junction considered highly reliable for signal transmission?
It has a high density of acetylcholine receptors, abundant vesicles, and structural features like junctional folds that ensure effective neurotransmitter binding and signal propagation.
What are the clinical manifestations of myasthenia gravis?
Symptoms include muscle weakness, especially in the eyes and eyelids, difficulty swallowing, and fatigue with sustained activity.
How does an acetylcholinesterase inhibitor work to treat myasthenia gravis?
It prevents the breakdown of acetylcholine in the synaptic cleft, prolonging its action and improving muscle contraction.
What electrical events differentiate ligand-gated and voltage-gated ion channels in the neuromuscular junction?
Ligand-gated channels respond to acetylcholine and initiate depolarization, while voltage-gated channels propagate the action potential along the muscle membrane.
How does the neuromuscular junction amplify the signal for muscle contraction?
By releasing large quantities of acetylcholine and activating numerous receptors, leading to a strong depolarization (end-plate potential) and a robust action potential.
What is temporal summation in the context of muscle twitches?
It is the additive effect of multiple action potentials arriving in rapid succession, increasing muscle contraction strength.
What is spatial summation, and how does it differ from temporal summation?
Spatial summation refers to multiple inputs converging on a single neuron, common in the CNS, while temporal summation involves the frequency of action potentials increasing contraction in a muscle fiber.
Why does the neuromuscular junction have such a high density of acetylcholine receptors?
To ensure that the large amount of acetylcholine released can reliably trigger a strong and rapid depolarization.
How does calcium signaling differ presynaptically and postsynaptically in the neuromuscular junction?
Presynaptically, calcium influx triggers vesicle fusion and neurotransmitter release. Postsynaptically, calcium released from the sarcoplasmic reticulum activates contraction.
What happens to the sarcoplasmic reticulum after muscle contraction is completed?
Calcium is pumped back into the sarcoplasmic reticulum by calcium pumps, terminating the contraction and resetting the system.
What is the typical time course of a synaptic event at the neuromuscular junction?
The neurotransmitter release and postsynaptic depolarization last about 1 millisecond.
How does the neuromuscular junction prevent overstimulation of muscle fibers?
Acetylcholine is rapidly broken down by acetylcholinesterase, terminating the signal.
What is the purpose of the T-tubule system in muscle fibers?
It ensures the action potential reaches deep into the muscle fiber.
What is the purpose of the T-tubule system in muscle fibers?
It ensures the action potential spreads deep into the muscle, activating contraction mechanisms throughout the fiber.
What structural feature of the neuromuscular junction facilitates high-frequency synaptic transmission?
Its large surface area, high receptor density, and extensive junctional folds optimize neurotransmitter binding and signal propagation.
