Excitation of Skeletal Muscle: Neuromuscular Transmission

An excitatory neurotransmitter released at the neuromuscular junction.

Specialized region of a muscle fiber membrane where nerve impulses are transmitted.

Membrane-bound sacs in axon terminals containing neurotransmitters.

Indentations in the muscle fiber membrane at the neuromuscular junction.

Channels in the muscle fiber membrane that open in response to acetylcholine.

Cellular organelles that provide energy (ATP) for cellular processes.

Adenosine triphosphate, the primary energy currency of the cell.

The gap between the axon terminal and muscle fiber membrane at the neuromuscular junction.

The connection between a nerve fiber and a muscle fiber.

Acetylcholine is rapidly broken down by the enzyme acetylcholinesterase in the synaptic space.

The enzyme acetylcholinesterase is primarily located in the spongy tissue of the synaptic space.

The tiny gap between the nerve terminal and the muscle fiber membrane.

Some acetylcholine diffuses out of the synaptic space and is no longer available to the muscle fiber.

Acetylcholine acts within the synaptic space for only a few milliseconds.

The invaginated membrane of the muscle fiber at the neuromuscular junction.

Prolonged muscle stimulation leads to fatigue at the neuromuscular junction.

Channels that open when an action potential arrives, allowing calcium ions to enter.

The brief presence of acetylcholine is sufficient to excite the muscle fiber.

The process by which vesicles release their contents outside the cell.

Rapid removal of acetylcholine prevents further muscle stimulation.

Over-excitation of synapses in the central nervous system also causes fatigue.

The accumulation of acetylcholine in the synaptic space, due to acetylcholinesterase inactivation, leads to repetitive stimulation of the muscle fiber and causes spasms.

Acetylcholine is synthesized in the cytosol of the nerve terminal but is immediately transported into synaptic vesicles. The vesicles store acetylcholine in a highly concentrated form, about 10,000 molecules per vesicle.

Calcium influx into the nerve terminal triggered by action potentials triggers the fusion of synaptic vesicles with the terminal membrane, releasing acetylcholine into the synaptic space.

Neostigmine inhibits acetylcholinesterase, preventing the breakdown of acetylcholine in the synaptic space. This leads to an increase in acetylcholine concentration.

D-tubocurarine is a curariform drug that blocks the action of acetylcholine on the muscle fiber acetylcholine receptors. This prevents the nerve impulse from being transmitted to the muscle.

Axoplasm is the cytoplasm within an axon. It is responsible for transporting substances, including synaptic vesicles, from the cell body to the nerve terminal.

Acetylcholinesterase is an enzyme that breaks down acetylcholine in the synaptic space, terminating the signal.

Diisopropyl fluorophosphate is a potent nerve gas poison that irreversibly inactivates acetylcholinesterase, leading to prolonged acetylcholine accumulation in the synaptic space. This results in severe muscle spasms and can be fatal.

Tiny tubes that run transverse to myofibrils, carrying action potentials deep into the muscle fiber.

A network of membrane-bound sacs that store and release calcium ions, triggering muscle contraction.

Voltage-sensitive proteins in the T tubules that detect changes in electrical potential.

Calcium release channels located on the sarcoplasmic reticulum that open in response to dihydropyridine receptors.

The process where an electrical signal (action potential) triggers muscle contraction.

T tubules run alongside the sarcoplasmic reticulum, and dihydropyridine receptors on the T tubules are linked to ryanodine receptor channels on the sarcoplasmic reticulum.

Calcium is released into the sarcoplasm surrounding the myofibrils, allowing the myosin heads to bind to actin filaments and initiate contraction.

Calcium pumps actively transport calcium back into the sarcoplasmic reticulum, ending the contraction.

Approximately 125 vesicles release their contents during a single action potential at the neuromuscular junction.

Acetylcholinesterase is the enzyme responsible for rapidly splitting acetylcholine into acetate ion and choline.

Choline, a product of acetylcholine breakdown, is actively reabsorbed back into the nerve terminal for reuse in synthesizing new acetylcholine.

Myasthenia gravis causes muscle weakness and paralysis due to antibodies that block or destroy acetylcholine receptors at neuromuscular junctions.

Clathrin is a protein responsible for forming 'coated pits' that pinch off the nerve terminal membrane, creating new synaptic vesicles.

Within about 20 seconds after each action potential, new vesicles form in the nerve terminal, ready to carry acetylcholine for subsequent release.

The nerve ending only has enough vesicles for a few thousand nerve-to-muscle impulses before needing replenishment.

In myasthenia gravis, the end plate potentials are too weak due to the reduced number of functional acetylcholine receptors, making muscle fiber depolarization difficult.

An enzyme that rapidly breaks down acetylcholine in the synaptic space, ensuring brief and controlled muscle stimulation.

Acetylcholine binds to receptors on the muscle fiber, causing depolarization and muscle contraction. However, it is immediately broken down by acetylcholinesterase, ensuring a brief and controlled response.

Mitochondria provide energy (ATP) for the synthesis of acetylcholine, the neurotransmitter responsible for muscle fiber excitation.

Acetylcholine-gated ion channels are positioned near the subneural clefts to ensure efficient transmission of the nerve impulse to the muscle fiber. Acetylcholine released from the nerve terminal diffuses across the synaptic space and interacts with these channels, triggering muscle fiber excitation.

Binding of two acetylcholine molecules to the alpha subunit proteins of the acetylcholine-gated ion channel causes a conformational change, opening the channel and allowing ions to flow across the muscle fiber membrane, leading to muscle fiber excitation.

Calcium ions influx into the nerve terminal, triggered by an action potential, stimulate the fusion of synaptic vesicles containing acetylcholine with the nerve terminal membrane. This process, called exocytosis, releases acetylcholine into the synaptic space.

Acetylcholinesterase, an enzyme located in the synaptic space, rapidly breaks down acetylcholine into acetate and choline. This rapid removal prevents continued stimulation of the muscle fiber.

Neostigmine inhibits acetylcholinesterase, preventing the breakdown of acetylcholine in the synaptic space. This leads to increased acetylcholine levels and prolonged muscle stimulation.

The dense bar area, located on the muscle fiber membrane, is where the acetylcholine-gated ion channels are concentrated. This area is positioned directly below the nerve terminal, facilitating efficient interaction between acetylcholine and the channels.

The acetylcholine-gated ion channel remains closed until two acetylcholine molecules bind to the alpha subunit proteins. This binding triggers a conformational change in the channel, opening it and allowing ions to pass through.

Acetylcholinesterase binds to and splits the acetylcholine molecule into inactive fragments, preventing further stimulation of the muscle fiber by acetylcholine.

Rapid breakdown of acetylcholine prevents continuous muscle stimulation, allowing for precise and controlled movements. It also prevents muscle fatigue from overstimulation.

If acetylcholinesterase is blocked, acetylcholine accumulates in the synaptic cleft, leading to prolonged muscle stimulation. This can cause muscle spasms, weakness, and even paralysis.

Prolonged muscle stimulation leads to fatigue at the neuromuscular junction. This happens when the synapses are overexcited, resulting in a decrease in the ability to transmit signals.

The arrival of an action potential at the nerve terminal causes voltage-gated calcium channels to open. This allows calcium ions to flow into the nerve terminal, which triggers the fusion of synaptic vesicles with the presynaptic membrane, releasing acetylcholine into the synaptic cleft.

Acetylcholine diffuses across the synaptic cleft and binds to receptors on the muscle fiber membrane, causing these receptors to open.

The binding of acetylcholine to its receptors opens ion channels, allowing sodium ions to flow into the muscle fiber. This influx of sodium ions creates a local positive potential change inside the muscle fiber membrane, called the end plate potential.

The end plate potential is a local depolarization of the muscle fiber membrane at the neuromuscular junction. It's a localized change in electrical potential caused by the influx of sodium ions. The end plate potential initiates an action potential that travels down the muscle fiber, triggering muscle contraction.

1. Action potential arrives at the nerve terminal. 2. Calcium ions enter the terminal. 3. Acetylcholine is released into the synaptic cleft. 4. Acetylcholine binds to receptors on the muscle fiber. 5. Sodium ions flow into the muscle fiber, creating the end plate potential. 6. The end plate potential triggers an action potential in the muscle fiber, causing muscle contraction.

Acetylcholine is rapidly broken down by the enzyme acetylcholinesterase in the synaptic cleft. This ensures that the muscle fiber is not continuously stimulated and allows for precise control of muscle contraction.

Calcium ions play a crucial role in triggering muscle contraction. They are released from the sarcoplasmic reticulum and bind to troponin, causing a conformational change in the troponin-tropomyosin complex that exposes the myosin-binding sites on actin filaments, allowing muscle contraction to occur.

1. The action potential travels down the T-tubules. 2. The action potential triggers the release of calcium ions from the sarcoplasmic reticulum. 3. Calcium ions bind to troponin, causing a conformational change. 4. The myosin-binding sites on actin are exposed. 5. Myosin heads bind to actin, causing a power stroke and muscle contraction.

Contraction is terminated when calcium ions are pumped back into the sarcoplasmic reticulum, reducing the calcium concentration in the sarcoplasm and allowing the troponin-tropomyosin complex to block myosin-binding sites on actin.

The degree to which the normal stimulus at a neuromuscular junction exceeds the minimum required to trigger muscle contraction. It indicates how much reserve capacity exists for successful nerve transmission.

A bacterial poison that blocks the release of acetylcholine at the neuromuscular junction, preventing muscle contraction and leading to paralysis.

Calcium ions influx into the nerve terminal upon action potential arrival triggers the fusion of synaptic vesicles containing acetylcholine with the terminal membrane, releasing acetylcholine into the synaptic space.

Rapid breakdown of acetylcholine by acetylcholinesterase is crucial to ensure the termination of muscle stimulation and prevent prolonged muscle contraction.

Botulinum toxin prevents the release of acetylcholine from the nerve terminal, leading to muscle paralysis by blocking the signals that normally trigger contraction.

A high safety factor ensures reliable muscle activation even under conditions of reduced acetylcholine release or receptor sensitivity, ensuring a smooth and predictable muscle response.

Prolonged muscle stimulation can lead to neuromuscular junction fatigue, characterized by decreased signal transmission due to reduced acetylcholine release or receptor sensitivity.

Acetylcholinesterase rapidly breaks down acetylcholine in the synaptic space, preventing prolonged muscle stimulation and allowing the muscle to relax between nerve impulses.

The acetylcholine-gated channel is about 0.65 nanometers in diameter, allowing the passage of positive ions like sodium (Na+), potassium (K+), and calcium (Ca++) but preventing negative ions like chloride ions due to strong negative charges at the channel opening.

More sodium ions (Na+) flow through the acetylcholine-gated channels than other ions because:

1. Sodium ions are abundant outside the muscle cell, while potassium ions are abundant inside.
2. The negative potential inside the muscle membrane attracts positive sodium ions.

Rapid removal of acetylcholine prevents further stimulation of the muscle fiber, preventing fatigue by allowing time for the muscle to relax.

Neostigmine is a drug that inhibits acetylcholinesterase, preventing the breakdown of acetylcholine. This leads to increased acetylcholine levels and prolonged muscle stimulation.

D-Tubocurarine blocks the action of acetylcholine on the muscle fiber receptors, preventing nerve impulses from reaching the muscle. This leads to muscle paralysis.

A localized positive potential change inside the muscle fiber membrane at the neuromuscular junction, caused by the influx of sodium ions when acetylcholine-gated channels open.

The end plate potential, a local depolarization at the neuromuscular junction, triggers an action potential that travels along the muscle fiber membrane, ultimately leading to muscle contraction.

Sodium ions entering the muscle fiber through acetylcholine-gated channels create a positive charge inside the muscle fiber membrane, resulting in the end plate potential.

Opening acetylcholine-gated channels allows a large influx of sodium ions into the muscle fiber, creating a positive change in the electrical potential inside the fiber, known as the end plate potential.

Acetylcholine, upon binding to its receptors on the muscle fiber membrane, causes the acetylcholine-gated channels to open, allowing sodium ions to flow into the muscle fiber.

The end plate potential is crucial for initiating muscle contraction. It is the local depolarization that triggers the action potential traveling along the muscle fiber, ultimately leading to the contraction.

A high safety factor ensures reliable muscle activation even when there's reduced acetylcholine release or receptor sensitivity, leading to smooth and predictable muscle responses.

Acetylcholinesterase rapidly breaks down acetylcholine in the synaptic space, preventing prolonged muscle stimulation and ensuring precise control of muscle contraction.

Prolonged muscle stimulation can lead to neuromuscular junction fatigue, characterized by a decrease in signal transmission due to reduced acetylcholine release or receptor sensitivity.

Acetylcholine is stored in synaptic vesicles within the nerve terminal.

Calcium influx into the nerve terminal triggers the fusion of vesicles with the terminal membrane, releasing acetylcholine.

D-tubocurarine blocks acetylcholine receptors on the muscle fiber, preventing nerve impulses from reaching the muscle.

Diisopropyl fluorophosphate is a deadly nerve gas that permanently inactivates acetylcholinesterase, leading to prolonged muscle stimulation and potential death.

Acetylcholine formation and release at the neuromuscular junction involve:

1. Vesicle formation by the Golgi apparatus in the motoneuron.
2. Acetylcholine synthesis and packaging into vesicles.
3. Vesicle transport to the nerve terminal.
4. Calcium-dependent vesicle fusion and acetylcholine release.

Acetylcholine binds to receptors on the muscle fiber membrane, causing depolarization. This depolarization triggers an action potential that travels along the muscle fiber, causing muscle contraction.

Drugs like methacholine, carbachol, and nicotine act like acetylcholine, causing depolarization of the muscle fiber membrane. They are not destroyed by cholinesterase or are destroyed slowly, resulting in prolonged action.

Neostigmine, physostigmine, and diisopropyl fluorophosphate inactivate acetylcholinesterase, preventing the breakdown of acetylcholine. This leads to prolonged muscle stimulation and possible spasms.

The safety factor is how much the normal stimulus exceeds the minimum required to trigger muscle contraction. It reflects the reserve capacity for successful nerve transmission.

Botulinum toxin blocks the release of acetylcholine from the nerve terminal, preventing muscle contraction and leading to paralysis.

Rapid removal of acetylcholine prevents continuous muscle stimulation, allowing for precise and controlled movements. It also prevents muscle fatigue from overstimulation.

Myasthenia Gravis is a disease where antibodies attack acetylcholine receptors at the neuromuscular junction. This leads to muscle weakness and fatigue as nerve impulses are not transmitted effectively.

The neuromuscular junction can adapt to repeated stimulation by: - Recycling vesicles: Vesicles are quickly recycled after releasing acetylcholine, allowing for continued transmission. - Increasing acetylcholine synthesis: The nerve terminal increases acetylcholine production to meet demand. - Recruiting more motor units: More muscle fibers are activated to create more force. - Slight reduction in sensitivity: The receptors become slightly less sensitive, but this allows for continued stimulation without fatigue.

An enzyme that rapidly breaks down acetylcholine, ensuring a brief and controlled muscle contraction by preventing prolonged stimulation.

Acetylcholine is rapidly removed from the synaptic space to prevent continuous muscle stimulation, allowing for precise control of muscle contraction and preventing fatigue.

When acetylcholine binds to receptors on the muscle fiber, it opens ion channels, allowing sodium ions to flow into the muscle fiber. This influx of sodium ions creates a local positive potential change inside the muscle fiber membrane, called the end plate potential.

The end plate potential is a localized depolarization of the muscle fiber membrane at the neuromuscular junction. It's initiated by the influx of sodium ions, triggering an action potential that travels down the muscle fiber.

Botulinum toxin prevents the release of acetylcholine from the nerve terminal, leading to muscle paralysis by blocking the signals that normally trigger contraction.

The safety factor is the degree to which the normal stimulus at a neuromuscular junction exceeds the minimum required to trigger muscle contraction. A high safety factor ensures reliable muscle contraction even under less-than-optimal conditions.

Calcium ions influx into the nerve terminal upon action potential arrival triggers the fusion of synaptic vesicles containing acetylcholine with the terminal membrane, releasing acetylcholine into the synaptic space.

1. Action potential arrives at the nerve terminal. 2. Calcium ions enter the terminal. 3. Acetylcholine is released into the synaptic cleft. 4. Acetylcholine binds to receptors on the muscle fiber. 5. Sodium ions flow into the muscle fiber, creating the end plate potential. 6. The end plate potential triggers an action potential in the muscle fiber, causing muscle contraction.