Sliding Filament Theory & Muscle Contraction - Vocabulary Flashcards

Structure of Skeletal Muscle and Core Components

• Skeletal muscles are voluntary and are organized into fascicles, which are bundles of muscle fibers. Inside each fiber are long, rod-like organelles called myofibrils, making up most of the visible muscle.

• Myofibrils contain the contractile units called sarcomeres, which are arranged in series along the length of the myofibril and give skeletal muscle its striated appearance.

• The muscle fiber’s plasma membrane is the sarcolemma; invaginations called transverse tubules (T-tubules) penetrate the cell and wrap around each myofibril.

• The sarcoplasmic reticulum (SR) surrounds each myofibril and stores calcium (Ca²⁺); Ca²⁺ release into the cytoplasm triggers contraction.

• Mitochondria within muscle fibers provide energy (ATP) for contraction.

• The basic fiber cytoplasm is the sarcoplasm; T-tubules transmit action potentials from the sarcolemma to the SR to coordinate Ca²⁺ release.

• The sarcolemma contains voltage-gated channels that participate in depolarization and signal propagation along the muscle fiber.

• A typical muscle fiber contains thousands to tens of thousands of sarcomeres in series, producing the overall contraction observed.

Sarcomere Structure and the Myofilaments

• The sarcomere is the functional contractile unit of skeletal muscle; it runs from one Z-disc (Z-line) to the next.

• Major filaments:

  • Thick filaments: myosin

  • Thin filaments: actin

• Regulatory proteins:

  • Tropomyosin: a long, filamentous protein that blocks myosin-binding sites on actin when the muscle is relaxed.

  • Troponin: a complex of three subunits (typically discussed as troponin C, I, T) that regulates tropomyosin position in response to Ca²⁺.

• Key sarcomere landmarks:

  • A-band (anisotropic): contains the entire length of the thick filaments; in contraction the A-band length remains the same.

  • I-band (isotropic): contains only thin filaments; shortens during contraction.

  • H-zone: central part of the A-band containing only thick filaments; shortens/disappears during contraction.

  • Z-line (Z-disc): anchors actin filaments and defines sarcomere boundaries.

  • M-line: center of the sarcomere; holds the thick filaments together.

• Filaments interact via cross-bridges: protruding heads of myosin form cross-bridges with actin during contraction.

• The I-band and H-zone decrease in length during contraction; the A-band remains constant.

Regulatory Proteins and Calcium

• Calcium (Ca²⁺) is stored in the sarcoplasmic reticulum and released in response to an action potential.

• Ca²⁺ binds to troponin, causing a conformational change that moves tropomyosin away from myosin-binding sites on actin, exposing the active sites.

• This exposure allows myosin heads to bind to actin, enabling the cross-bridge cycle and contraction.

Excitation-Contraction Coupling: The Path from Nerve to Muscle

• Neuromuscular junction (NMJ) events initiate contraction:

  • A nerve impulse reaches the axon terminal of a motor neuron.

  • Synaptic vesicles release acetylcholine (ACh) into the synaptic cleft via exocytosis.

  • ACh binds to receptors on the motor end plate, opening ion channels and depolarizing the sarcolemma.

  • The depolarization travels along the sarcolemma and down the T-tubules.

  • The signal propagates to the sarcoplasmic reticulum (SR) via voltage-gated channels, triggering Ca²⁺ release into the cytoplasm (sarcoplasm).

  • Ca²⁺ initiates the excitation-contraction sequence by enabling actin-myosin interaction after troponin-tropomyosin rearrangement.

• Calcium release and the EC coupling process convert an electrical signal into a mechanical response, enabling contraction.

• Acetylcholine action is terminated by acetylcholinesterase, which stops further stimulation at the NMJ and allows relaxation to begin.

The Cross-Bridge Cycle (Contraction Cycle)

• In the resting state, myosin heads are energized in the cocked, high-energy position (pre-stroke) due to ATP hydrolysis.

• Step-by-step sequence during contraction (phase 2 in the lecture):

  • Cross-bridge formation: energized myosin head binds to a binding site on actin to form a cross-bridge. ext{Myo{ }ADP{+}Pi + Actin}
    ightarrow ext{Cross-bridge}

  • Power stroke: the myosin head pivots, pulling the actin filament toward the M-line; ADP and Pi are released.

  • Cross-bridge detachment: ATP binds to myosin, reducing its affinity for actin, and the myosin head detaches from actin.

  • Cocking of the myosin head: hydrolysis of ATP to ADP + Pi re-energizes (cocks) the myosin head, returning it to the pre-stroke high-energy position.

• The cycle repeats as long as Ca²⁺ remains elevated and ATP is available.

• The contraction cycle can proceed for several seconds to minutes, depending on energy supply and Ca²⁺ availability.

Phases of Muscle Contraction

• Phase 1: Neuromuscular junction (initiation)

  • Nerve impulse arrival at NMJ triggers ACh release and NMJ depolarization.

  • ACh binding opens Na⁺ channels, generating an action potential that travels along the sarcolemma and into T-tubules.

  • This leads to Ca²⁺ release from the SR and initiation of EC coupling.

• Phase 2: Excitation-contraction coupling and cross-bridge cycling (contraction)

  • Ca²⁺ binds to troponin; tropomyosin moves away from actin’s myosin-binding sites.

  • Cross-bridge formation occurs; the cycle repeats with the power stroke and detachment steps driven by ATP hydrolysis.

• Phase 3: Relaxation

  • Acetylcholinesterase breaks down ACh, stopping the neural signal.

  • Ca²⁺ is pumped back into the SR, Ca²⁺ concentration in the cytoplasm falls, active sites are re-blocked by tropomyosin, cross-bridges detach, and the muscle relaxes.

• Contraction continues as long as Ca²⁺ remains elevated and ATP is available; relaxation occurs when Ca²⁺ is removed and cross-bridges cannot form.

Energy for Muscle Contraction: Three Systems

• Creatine phosphate (CP) system (phosphocreatine, CP):

  • Reaction: ext{CP} + ext{ADP}
    ightarrow ext{ATP} + ext{Cr}

  • Provides immediate, short-term energy for rapid, high-intensity activities (e.g., sprinting).

  • Limited capacity: typically exhausted in about 10–15 seconds of maximal effort; yields about 1 ATP per CP molecule.

  • CP is rapidly depleted; ATP must then be produced by other systems.

  • CP acts as a rapid, immediate energy source that bridges to longer-duration energy systems.

• Anaerobic (glycolytic) system: glycolysis with fermentation when O₂ is limited

  • Glycolysis occurs in the cytoplasm, outside mitochondria, and can function with or without oxygen.

  • Glucose → 2 pyruvate + net 2 ATP (per glucose) + NADH; when oxygen is scarce, pyruvate is reduced to lactate (lactic acid fermentation).

  • Lactic acid buildup can occur with intense, short-duration exercise, causing the burning sensation and fatigue.

  • Lactate can diffuse into the bloodstream and be taken up by the liver, heart, or other tissues; liver can convert lactate back to glucose (Cori cycle).

  • Typical duration: used for activities around 30 seconds to 2 minutes; provides rapid but limited energy.

• Aerobic (oxidative) system: cellular respiration with oxygen

  • Occurs in mitochondria; includes glycolysis (cytoplasm), pyruvate oxidation to acetyl-CoA, Krebs cycle (citric acid cycle), and electron transport chain (ETC).

  • Overall reaction (glucose + O₂ → CO₂ + H₂O + ATP):
    ext{C}6 ext{H}{12} ext{O}6 + 6 ext{O}2
    ightarrow 6 ext{CO}2 + 6 ext{H}2 ext{O} + ext{ATP}

  • ATP yield per glucose is high (approximately 30–34 ATP, depending on shuttle systems and efficiency).

  • Primary energy source for sustained, endurance activities (e.g., long-distance running, cycling).

  • Stages:

  • Glycolysis (cytoplasm): net 2 ATP per glucose, 2 NADH.

  • Pyruvate oxidation to acetyl-CoA and the Krebs cycle in mitochondria: yields NADH, FADH₂, and GTP/ATP.

  • Electron transport chain (mitochondrial inner membrane): oxidative phosphorylation yields the majority of ATP (via NADH and FADH₂).

• Comparative summary (rate vs capacity):

  • CP system: very fast rate, very low capacity; peak, short-duration energy.

  • Anaerobic glycolysis: fast rate, moderate capacity; useful for ~30 seconds to 2 minutes.

  • Aerobic respiration: slower rate, high capacity; supports long-duration activity.

• Typical ATP yields (for reference):

  • CP system: ~1 ATP per CP molecule transferred to ADP.

  • Anaerobic glycolysis: net ~2 ATP per glucose; produces lactate when O₂ is limited.

  • Aerobic respiration (per glucose): ~30–34 ATP total (2 from glycolysis, ~2 from Krebs, ~26–28 from ETC).

• Practical notes:

  • The three systems work together; during different activities, one system may dominate depending on duration and intensity.

  • Pyruvate fate (conversion to acetyl-CoA) depends on oxygen availability; under anaerobic conditions, pyruvate becomes lactate.

  • The liver and other tissues participate in lactate clearance and glucose regeneration during recovery.

Key Concepts and Takeaways

• The sliding filament theory explains contraction via actin-myosin interactions powered by ATP; the myofilaments slide past each other shortening the sarcomere.

• The A-band remains constant in length during contraction; the I-band and H-zone shorten as actin slides over myosin toward the M-line.

• The neuromuscular junction is the start of contraction: motor neuron action potential triggers ACh release, which excites the muscle fiber and leads to Ca²⁺ release from the SR.

• Ca²⁺ is the crucial trigger for exposing myosin-binding sites on actin; without Ca²⁺ or ATP, contraction cannot proceed.

• The cross-bridge cycle continues as long as Ca²⁺ is present and ATP is available, enabling repeated power strokes.

• Energy systems differ in speed and capacity: CP provides immediate energy, anaerobic glycolysis provides rapid energy with lactate byproduct, and aerobic respiration provides large amounts of energy over longer durations.

• ATP is the universal energy currency; its sustained production requires careful coordination of signaling, ion homeostasis, and metabolic pathways.

Quick Reference: Common Equations and Concepts (LaTeX)

• ATP hydrolysis (energy release):
  ext{ATP}
  ightarrow ext{ADP} + ext{Pi} + ext{energy}

• Creatine phosphate system (rapid ATP production):
  ext{CP} + ext{ADP}
  ightarrow ext{ATP} + ext{Cr}

• Glycolysis (net):
  ext{Glucose} + 2 ext{NAD}^+ + 2 ext{ADP} + 2 ext{Pi}
  ightarrow 2 ext{Pyruvate} + 2 ext{NADH} + 2 ext{ATP} + 2 ext{H}_2 ext{O} + 2 ext{H}^+

• Pyruvate oxidation to acetyl-CoA:
  ext{Pyruvate} + ext{CoA} + ext{NAD}^+
  ightarrow ext{Acetyl{-}CoA} + ext{CO}_2 + ext{NADH}

• Krebs cycle (per acetyl-CoA):
  ext{Acetyl{-}CoA}
  ightarrow 2 ext{CO}2 + 3 ext{NADH} + 1 ext{FADH}2 + ext{GTP (ATP)}

• Electron transport chain yield (approximate, per glucose):
  ext{NADH}
  ightarrow ext{~2.5 ATP}, ext{FADH}_2
  ightarrow ext{~1.5 ATP} \ ext{Total}
  ightarrow ext{~30–34 ATP}

• Overall aerobic respiration (glucose + O₂):
  ext{C}6 ext{H}{12} ext{O}6 + 6 ext{O}2
  ightarrow 6 ext{CO}2 + 6 ext{H}2 ext{O} + ext{ATP}

• Lactic acid fermentation (anaerobic):
  ext{Pyruvate} + ext{NADH}
  ightarrow ext{Lactate} + ext{NAD}^+

Connections to Practice and Real-World Relevance

• Understanding these mechanisms helps explain why athletes train to optimize different energy pathways (sprint vs. endurance) and how fatigue develops with Ca²⁺ depletion, lactic acid buildup, or ATP depletion.

• The Cori cycle illustrates how lactate produced in working muscles is reused by the liver to generate glucose, highlighting metabolic cooperation across organs.

• The regulation of contraction is a finely tuned process involving electrical signaling, ion dynamics, protein conformation changes, and energy supply—central to physiology and medicine.

Review Prompts

• Draw and label a sarcomere, identifying Z-line, M-line, I-band, A-band, and H-zone. Explain which bands shorten during contraction and which stay the same.

• List the three energy systems for muscle contraction and compare their rate, capacity, fuel source, and typical activity examples.

• Describe the steps of excitation-contraction coupling from NMJ to Ca²⁺ release and cross-bridge cycling.

• Explain the cross-bridge cycle in order, including what triggers each step and the role of ATP.

• Explain how Ca²⁺ and regulatory proteins (troponin and tropomyosin) control contractile activation.

• Outline the process of relaxation, including the role of acetylcholinesterase and Ca²⁺ reuptake.

• Provide the chemical equations for CP system, glycolysis, and aerobic respiration, and state approximate ATP yields.

• Discuss how lactate is produced and how it can be recycled or disposed of in the body.