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What is the sliding filament theory of muscle contraction?
It states that thick and thin filaments slide past each other without shortening
What do the myosin crossbridges do during contraction?
Attach cyclically to actin and generate force by pulling thin filaments
What is the function of ATP in crossbridge cycling?
ATP provides the energy for myosin to detach and reattach to actin
Which band shortens during muscle contraction?
I-band and H-zone
Which band remains the same length during contraction?
A-band
What is the Z-line?
The boundary of the sarcomere to which thin filaments are anchored
What is titin?
An elastic protein that extends from M-line to Z-line, contributing to passive elasticity
What is nebulin believed to do?
Act as a molecular ruler for thin filament length
What defines the H-zone?
Region in A-band with no thin-thick filament overlap
What is the sarcolemma?
The plasma membrane surrounding a muscle fiber
What are T-tubules?
Invaginations of the sarcolemma that conduct action potentials into the muscle fiber
What is the sarcoplasmic reticulum (SR)?
A membrane system that stores and releases calcium for contraction
What forms a triad in skeletal muscle?
A T-tubule flanked by two terminal cisternae of the SR
How is the excitation signal carried into the muscle interior?
Via T-tubules propagating an action potential
What does depolarization of the T-tubule cause in skeletal muscle?
Direct opening of Ca²⁺ release channels (RyR1) on the SR
What triggers calcium release in cardiac muscle?
Influx of extracellular Ca²⁺ via DHPR opens RyR2 on SR
What type of calcium release occurs in skeletal muscle?
Mechanically-gated release via voltage-sensor coupling
What type of calcium release occurs in cardiac muscle?
Calcium-induced calcium release
What protein resequesters calcium into the SR after contraction?
SR Ca²⁺-ATPase (SERCA pump)
What is the main component of thick filaments?
Myosin
What is the main component of thin filaments?
Actin
What part of myosin forms the crossbridges?
The globular heads
What is the structure of actin filaments?
Two helical chains of actin subunits
What activates myosin's ATPase activity?
Binding to actin
What is the first step in the crossbridge cycle?
ATP binds to myosin, causing detachment from actin
What happens after ATP hydrolysis by myosin?
The crossbridge becomes energized and reorients
What allows myosin to bind actin again?
Presence of Ca²⁺ exposes binding sites on actin
What causes the power stroke in the crossbridge cycle?
Release of ADP and Pi from myosin
What causes myosin to detach from actin again?
Binding of a new ATP molecule
What is the rate-limiting step in the cycle?
Dissociation of ADP and Pi
How does actin accelerate myosin's ATPase cycle?
It speeds up dissociation of ADP and Pi from myosin
What triggers contraction in skeletal and cardiac muscle?
Increase in sarcoplasmic Ca²⁺ concentration
What protein complex regulates actin-myosin interaction in skeletal and cardiac muscle?
Troponin-tropomyosin complex
What does the troponin-tropomyosin complex do in the absence of calcium?
Inhibits actomyosin ATPase by preventing myosin from binding actin
What are the three subunits of troponin?
TnI, TnC, TnT
What is the function of TnI?
Inhibits ATPase activity of actomyosin
What is the function of TnC?
Binds calcium and relieves inhibition by TnI
What is the function of TnT?
Links TnI and TnC to tropomyosin
Where are troponin and tropomyosin located?
On thin filaments
How does tropomyosin inhibit contraction?
It blocks myosin binding sites on actin when Ca²⁺ is low
What happens to tropomyosin when Ca²⁺ binds to troponin?
It shifts position to expose myosin binding sites on actin
How many actin monomers are regulated by each troponin-tropomyosin unit?
Seven
What shape is tropomyosin?
Coiled-coil protein made of two α-helices
What occurs when myosin binding sites are exposed on actin?
Crossbridge cycling and contraction proceed
What happens to the position of tropomyosin when Ca²⁺ is added?
It moves from a blocking to an exposing position on actin
What disease can result from sarcomeric protein mutations?
Familial Hypertrophic Cardiomyopathy
What happens to sarcomeric proteins in certain genetic mutations?
They develop point mutations that can lead to cardiomyopathies
What is a common sarcomere-related disease affecting young adults?
Familial Hypertrophic Cardiomyopathy
What percent of individuals are affected by sarcomeric protein mutations?
Approximately 1 in 250
What regulatory strategy could potentially treat sarcomeric mutation-related diseases?
Modulating thin filament Ca²⁺ sensitivity or controlling myosin crossbridge recruitment
What triggers thin filament movement in muscle contraction?
Calcium binding to troponin, shifting tropomyosin
What molecular event stops contraction and promotes relaxation?
Resequestration of Ca²⁺ into the sarcoplasmic reticulum via Ca²⁺-ATPase
How is myosin ATPase activity related to contraction?
It provides energy for crossbridge cycling
How does actin influence myosin ATPase activity?
Actin accelerates the rate-limiting step of the ATPase cycle