MPP: BLOCK 2: SKELETAL MUSCLE PHYSIOLOGY

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Questions and Answers

What is the primary function of SERCA pumps in muscle cells?

Facilitating the entry of calcium ions into the sarcomere

Generating action potentials in muscle fibers

Removing calcium ions from the cytoplasm and storing them (correct)

Releasing calcium ions from the sarcoplasmic reticulum

What is the significance of the T-tubule system in muscle contraction?

It helps carry action potentials directly into the muscle fibers (correct)

It enhances the storage of glycogen in muscle cells

It provides structural support to the muscle fibers

It regulates the blood supply to the muscle tissue

Which ion's gradient is crucial for generating the action potentials in muscle fibers?

Sodium ($Na^+$) (correct)

Potassium ($K^+$)

Calcium ($Ca^{2+}$)

Chloride ($Cl^-$)

Which of the following best describes the role of calcium ions during muscle contraction?

They bind to tropomyosin, allowing actin-myosin interaction Signup and view all the answers

What condition is characterized by an autoimmune attack affecting neuromuscular transmission?

Myasthenia gravis Signup and view all the answers

How does the loss of dystrophin function impact muscle cells?

It prevents the anchoring of the contractile array to the cytoskeleton Signup and view all the answers

During muscle contraction, what happens to the sarcomere length?

It shortens as the thick and thin filaments slide past each other Signup and view all the answers

What is the primary ion responsible for the release of neurotransmitters at the neuromuscular junction?

Calcium ($Ca^{2+}$) Signup and view all the answers

Which condition is primarily linked with a recessive X-linked mutation in the dystrophin gene?

Duchenne muscular dystrophy Signup and view all the answers

What does a decrease in cross-bridge formation potential refer to in muscle mechanics?

Increased muscle fatigue and lowered contraction force Signup and view all the answers

What is the primary function of the SERCA pump in skeletal muscle?

To transport calcium ions back into the sarcoplasmic reticulum Signup and view all the answers

Which ion is crucial for the event of depolarization at the neuromuscular junction?

Sodium (Na+) Signup and view all the answers

What determines the characteristics of an action potential in skeletal muscle fibers?

Ion concentration gradients across the membrane Signup and view all the answers

Which transport mechanism is primarily responsible for maintaining the ion gradients necessary for membrane potential in skeletal muscle cells?

Active transport Signup and view all the answers

Which of the following best describes Myasthenia Gravis's impact on neuromuscular transmission?

Antibody-mediated blockade of acetylcholine receptors Signup and view all the answers

What role do troponin and tropomyosin play in the sarcomere?

They regulate the exposure of myosin binding sites on actin Signup and view all the answers

During excitation-contraction coupling, which ion's rise is primarily responsible for triggering muscle contraction?

Calcium (Ca++) Signup and view all the answers

What is the role of the Z disks in the sarcomere?

To anchor thin filaments Signup and view all the answers

In the context of skeletal muscle contraction, what is preload?

The stretching of muscle before contraction begins Signup and view all the answers

What mechanism leads to the release of calcium ions from the sarcoplasmic reticulum during muscle contraction?

Action potentials traveling down the T-tubules Signup and view all the answers

What is the primary function of the neuromuscular junction (NMJ)?

Facilitate communication between motor neurons and muscle fibers Signup and view all the answers

Which ion is relatively high inside the muscle cell compared to outside?

K+ Signup and view all the answers

What is the role of calcium in excitation-contraction coupling?

It triggers muscle fiber contraction Signup and view all the answers

What condition is characterized by antibodies against nicotinic acetylcholine receptors?

Myasthenia Gravis Signup and view all the answers

How does the membrane potential change during an action potential?

It becomes more positive during depolarization Signup and view all the answers

What triggers calcium release from the sarcoplasmic reticulum?

Propagation of the action potential down the T-tubules Signup and view all the answers

What effect does Myasthenia Gravis have on muscle function?

It causes variable muscle weakness Signup and view all the answers

What occurs during the depolarization phase of an action potential?

Sodium ions rapidly enter the cell Signup and view all the answers

Which mechanism primarily resets ion concentrations after an action potential in muscle cells?

Na+/K+ ATPase pump Signup and view all the answers

Which term describes the process of converting electrical signals to mechanical contraction?

Excitation-contraction coupling Signup and view all the answers

What is the result of the effective blockade of acetylcholine receptors in Myasthenia Gravis?

Decreased ability to generate muscle action potentials Signup and view all the answers

Which ion primarily drives out of the cell due to its chemical gradient?

Potassium (K+) Signup and view all the answers

What initiates the process of excitation-contraction coupling?

Release of acetylcholine at the NMJ Signup and view all the answers

Study Notes

Neuromuscular Junction (NMJ)

Autoimmune condition myasthenia gravis (MG) is the most common disorder affecting neuromuscular transmission
Antibodies against nicotinic acetylcholine receptors interfere with normal signaling at the NMJ
Muscle weakness varies greatly
Treatment includes anticholinesterase inhibitors

Ion Chemical Gradients

K+ is the only major ion that’s high inside a cell relative to outside
Chemical gradients drive K+ out of the cell
Na+, Cl- and Ca++ are driven into the cell by their chemical gradients

Membrane Potential Changes

Action potential characteristics occur across a plasma membrane
Membrane potential changes are used to signal in nerve cells and muscle cells

Tissue Specific Action Potentials

Differences in ion channels in the membrane can lead to different action potential characteristics
Neuron action potentials are different from cardiac action potentials due to differences in potassium and sodium channels

Excitation-Contraction Coupling

The spike triggered by ACh release at the NMJ propagates over the sarcolemma
Action potentials are electrical events
Contraction is mechanical
Transduction from electrical to mechanical occurs via “excitation–contraction coupling”
Excitation-contraction coupling starts when the AP enters the T tubules and encounters a triad

Calcium Delivery to Muscle Fibers

Depolarization of the plasma membrane is transmitted down T-tubules which leads to calcium release from the sarcoplasmic reticulum

T-tubule

T-tubules carry action potentials from cell surface to structures responsible for Ca++ release

Sarcoplasmic Reticulum

The sarcoplasmic reticulum contains SERCA pumps and Calsequestrin
The sarcoplasmic reticulum is a site of specialized sensors and ion channels for E-C coupling

Structural Proteins of the Sarcomere

α- Actinin binds the ends of thin filaments to the Z disks
Titin is a huge protein with one end attached to a Z-disk and the other to a thick filament
Titin acts as a spring, limiting how much the sarcomere can be stretched and centers the thick filaments within the sarcomere
Dystrophin is a large protein associated with Z-disks
Dystrophin anchors the contractile array to the cytoskeleton and surface membrane
Dystrophin also aligns the Z disk with disks in adjacent myofibrils and muscle fibers

Clinical Connection: Muscular Dystrophy

Duchenne muscular dystrophy results from a recessive X-linked mutation in the dystrophin gene
Loss of dystrophin function prevents the cytoskeleton and its embedded contractile machinery from attaching to the sarcolemma
The muscle fiber becomes necrotic causing muscle wasting
Patients eventually succumb to respiratory muscle failure

Cross-bridge Cycling

Cross bridge cycling involves the interaction of actin and myosin to produce muscle contraction
Cross-bridge cycling involves a series of steps that include the attachment of the myosin head to actin, the power stroke, the detachment of the myosin head from actin and the re-energizing of the myosin head

Calcium Regulation of Skeletal Muscle Contraction

Calcium ions bind to troponin
Troponin causes a conformational change in tropomyosin revealing the myosin binding site on actin
Cross-bridge cycling can then occur, resulting in muscle contraction

Sliding Filaments

During muscle contraction the thin filaments slide past the thick filaments as myosin heads bind to actin
This sliding mechanism短縮させます短縮させます短縮させます shortens the sarcomere and the muscle

Skeletal Muscle Mechanics

Preload is the stretching of a muscle to optimize actin and myosin interaction
Sarcomere length is optimal in resting skeletal muscle
Stretching a sarcomere can prevent contraction if it physically separates the thick and thin filaments
Muscle performance peaks when the potential for crossbridge formation reaches a maximum

Organizational Hierarchy of Skeletal Muscle

Sarcoplasm is the cytoplasm of muscle cells
Sarcoplasm is rich in Mg2+, phosphates, and glycogen granules
Sarcoplasm contains high levels of myoglobin which is an oxygen-binding protein similar to hemoglobin
Sarcoplasm is dense with mitochondria closely alongside myofibrils to supply the lots of ATP for contraction

Skeletal Muscle Structure: Myosin

The main body of myosin is composed of two heavy chains
The head of myosin has ATPase activity which is where actin binding occurs
Each head region of myosin associates with two light chains: one regulatory light chain and one essential light chain
The neck of myosin is a hinge that allows the head to pivot and pull during contraction
The tail of myosin anchors the protein within a larger filamentous assembly
Two heavy chains intertwine to form a coiled coil
~100 assemblies form bundles
Two bundles are joined tail to tail to form a thick filament

Skeletal Muscle Structure: Actin

Each thin filament is composed of two strands of actin monomers wound into a helix
Tropomyosin acts as a blocking protein that covers the myosin binding sites on actin
Troponin is a calcium sensitive protein that uncovers the myosin binding site when Ca++ levels rise
TnC is the calcium sensing component of troponin
TnI inhibits actin/myosin interaction
TnT tethers troponin to tropomyosin

The Sarcomere is the Functional Unit of Skeletal Muscle

The sarcomere is defined between two Z disks
Z disks are proteinaceous plates that anchor thin filaments
The crossbridge is the region of overlap between the two types of filaments
The overlap between thick and thin filaments creates a distinct banding patterns

L9 Learning Objectives

Reproduce the hierarchical structure of skeletal muscle: From muscle fibers to myofibrils to sarcomeres, understand how each structure contributes to the overall function of skeletal muscle.
Explain the organization and compare and contrast the functions of myosin and actin: Be able to describe their structure, roles in cross-bridge cycling, and how they interact to produce muscle contraction.
Relate the clinical presentation of a disease to the importance of skeletal elements to the function of the sarcoplasm & sarcomere: Understand how diseases like muscular dystrophy impact the structure and function of the sarcomere.
Diagram the neuromuscular junction, list the steps of excitation, and characterize the important ions driving action potentials in skeletal muscle: Be able to describe how the nerve impulse is transmitted to the muscle cell, and the role of ions like calcium and sodium in this process.
Define the role of each “key player” in excitation-contraction coupling: Understand the role of the T-tubules, sarcoplasmic reticulum, calcium, and other proteins in translating the electrical signal to a mechanical contraction.
Diagram cross-bridge cycling : Visualize the steps involved in myosin head binding to actin, the power stroke, and detachment, all leading to muscle contraction.
Summarize the principle of preload and relate it to the sarcomere, thin filaments, and thick filaments: Explain how preload (the amount of stretch on a muscle) impacts its ability to generate force and why optimal sarcomere length is crucial for maximum contraction.

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Description

Explore the intricacies of the neuromuscular junction and the role of ion chemical gradients in muscle contractions and nerve signaling. This quiz covers the significance of potassium and sodium in membrane potentials as well as the distinctions between action potentials in neurons and cardiac cells. Test your understanding of these foundational physiological concepts.