Skeletal Muscle, L31 Flashcards

Excitable Tissue: Muscle

Learning Objectives

• Describe the events during excitation-contraction coupling.

• Describe ATP production via anaerobic and aerobic cellular respiration.

• Describe how muscle contraction is graded.

Skeletal Muscle: Neuromuscular Junction (NMJ)

• Action potential in motor nerve axon → neurotransmitter release at NMJ.

• Acetylcholine (ACh) activates receptors (ion channels).

• ACh receptors depolarize muscle membrane → action potential.

• Action potential → Calcium release from sarcoplasmic reticulum (SR).

Excitation-Contraction Coupling

• Resting muscle cell: Polarized (Vm ≈ -90 mV).

• Stimulation at NMJ: Rapid depolarization (Vm ≈ +40 mV) due to increased Na^+ permeability. Repolarization follows.

• Transient depolarization (action potential) is conducted via T-tubules to cause SR calcium channels to open.

• Myoplasmic calcium levels increase from 10^{-7} M to 10^{-5} M.

• Calcium pumped back into SR by Ca-ATPase (uses ATP).

• Calcium transient: Increase in calcium bound to troponin (TnCa).

• Troponin conformational change → tropomyosin movement → exposing actin filament's myosin binding sites.

• Myosin interacts with actin → cross-bridge cycling → contraction and force development.

• Calcium levels return to resting levels → inhibition of actin-myosin interaction → decreased force generation → relaxation.

• Twitch: Transient contraction in response to a single action potential (50-300 ms).

Muscle Metabolism

• ATP consumed during muscle contraction; muscle is a chemical motor.

• ATP levels controlled by aerobic/anaerobic metabolism.

• ATP supplied by:

  • Lohmann reaction: Creatine phosphokinase transfers phosphate from Creatine-Pi to ADP → ATP.

  • Adenylate kinase: 2 ADP → ATP + AMP.

• Steady-state oxidative metabolism in humans: ~300 watts of muscle power output.

• Short bursts of activity: Anaerobic pathways supply ATP; products removed by aerobic reactions.

• ATP is the "chemical currency" of the cell (Albert Szent-Györgyi).

• Glycolysis: 2 ATP per glucose (3 ATP if glycogen used) → pyruvate.

• Anaerobic metabolism: Pyruvate → lactate (end product).

  • Increases ATP yield by factor of 3.

  • Fast, but accumulation of products (protons, lactate) inhibits reactions (e.g., phosphofructokinase (PFK) in glycolysis).

  • Lactate metabolized by aerobic processes, consuming more oxygen.

• Oxidative metabolism: 36 ATP per glucose (6x more than anaerobic).

  • Slower, but cannot supply maximum energy demands of muscles.

Control of Muscle Tension

• Isotonic contraction: Tension remains constant while muscle length changes.

• Isometric contraction: Tension develops without change in muscle length.

• Motor unit: Motor neuron + all skeletal muscle fibers it stimulates.

• Muscle twitch: Brief contraction of all fibers in a motor unit in response to a single action potential.

• Control of muscle tension:

  1. Increasing frequency of stimulation (action potentials).

  2. Recruiting additional motor units.

Temporal Summation

• Action potential duration << calcium transient duration.

• Additional APs initiated before calcium levels return to resting levels.

• Calcium levels remain elevated → continuous force development.

• Temporal summation: Calcium transients summate, force rises until steady level (tetanus) is achieved.

• Force depends on stimulation rate and number of fibers.

Skeletal Muscle Fiber Types

• Muscle is not homogeneous; different fiber types exist with varying metabolic and myosin properties.

  • Type 1 (Slow Oxidative): Low ATPase rate, lower force production, mainly oxidative, high myoglobin/mitochondria (red color).

    • Extensive high-energy phosphate stores replenished by slow aerobic metabolism.

  • Type 2A (Fast Oxidative): High ATPase rate, high oxidative and glycolytic capacity, very high myoglobin/mitochondria (red color).

    • Small diameter facilitates oxygen diffusion.

  • Type 2B (Fast Glycolytic): High ATPase rate, low oxidative capacity, primarily glycolytic, low myoglobin/mitochondria (white color).

    • Large diameter fibers fatigue rapidly, generate large forces briefly.

Recruitment of Muscle Fibers

• Muscle contains many parallel muscle cells.

• Motor neuron innervates multiple fibers (motor unit).

• Increased force via recruitment of more motor units.

• Motor neuron innervates single fiber type.

• Small oxidative motor units recruited first.

• Force graded by number of motor units and neuron discharge rate.

• Oxidative fibers used for low-intensity exercise.

• Type 2 fibers recruited for short-duration, high-power output.

• Contractile function graded by motor unit recruitment.

• Size principle: Small oxidative motor units recruited first; fewer large glycolytic motor units recruited last.

• Fiber types can change based on stimulation.

• Physical training alters muscle composition via innervation and hypertrophy (increase in contractile proteins).

• Sustained use → muscle hypertrophy; reduced activity → muscle atrophy.

Length-Tension Relationship

• Isometric contraction.

• Maximum active force depends on actin-myosin overlap.

• Maximal force between 2.0 - 2.2 µm.

• Lengths >2.2 µm: Active forces decline due to reduced filament overlap.

• Lengths <2.0 µm: Filaments collide and interfere, reducing force.

• Total tension = active + passive force.

• Active Force: Developed via cross-bridge cycling; dependent on actin-myosin overlap.

• Passive Force: Increases as the muscle is stretched due to passive elements.

• Muscle has elastic components.

• Total tension is the sum of active and passive tension.

Excitation-Contraction Coupling

• Part 1: Neuromuscular junction

• Motor unit: A motor neuron and all the muscle fibers it innervates.

Steps:

1. ACh release:

   • Action potential travels down motor neuron.

   • Calcium channels open, Ca^{2+} enters axon terminal.

   • Vesicles fuse, releasing ACh into the synaptic cleft.

2. ACh receptor activation:

   • ACh binds to receptors on the muscle end plate.

   • Ligand-gated ion channels open, allowing Na^+ influx, making the cell less negative (end plate potential).

   • Acetylcholinesterase rapidly breaks down ACh.

3. Muscle Action Potential:

   • Sufficient ligand-gated channels open, reaching threshold.

   • Voltage-gated Na^+ channels open; action potential triggered.

   • Action potential propagates along sarcolemma into the T-tubule system.

• Part 2: Calcium coupling

1. Calcium release from SR:

   • Action potential travels down T-tubules.

   • Voltage-gated Ca^{2+} channels in SR open.

   • Ca^{2+} released into cytosol.

2. Ca^{2+} binds with troponin:

   • Ca^{2+} concentrations reach a critical threshold.

   • Myosin binding sites on actin filament are exposed.

   • Cross-bridge cycle occurs.

Cross-Bridge Cycle:

6. Cross-bridge formation.

7. Power stroke.

8. Detachment.

9. Energization of myosin head.

10. Contraction Ends:

    • Calcium is actively pumped back into the sarcoplasmic reticulum via Ca^{2+}-ATPase pumps.

    • Tropomyosin moves back covering the myosin binding site.

    • The muscle “twitch” is complete!

Muscle Metabolism: Sources of ATP

1. Creatine phosphate

2. Anaerobic glycolysis

3. Aerobic metabolism

• Creatine Phosphate

  • Energy source: creatine phosphate.

  • Creatine phosphate + ADP → creatine + ATP (1 ATP per cycle).

  • Creatine phosphate acts as ATP “store” but is quickly spent (<15s).

  • Anaerobic (no oxygen required).

• Anaerobic Glycolysis

  • Energy source: glucose.

  • Anaerobic = no oxygen required.

  • Fast but inefficient (2 ATP per glucose).

  • Good for short intense exercise.

  • Dominant system from about 10-30s of maximal effort.

  • Build-up of metabolites, e.g., H^+ limits duration to max 120s.

• Aerobic Metabolism

  • Energy source: Glucose, pyruvic acid, fatty acids, amino acids.

  • Efficient (32 ATP per glucose), but comparatively slow. Max 300 W.

  • Requires oxygen, therefore good blood supply.

  • Important for postural muscles and endurance exercise.

Muscle Fiber Types

• Type 1 (slow oxidative) - high in myoglobin for oxygen stores & mitochondria. Good for runners.

• Type 2 (fast twitch) - Sprinters/weightlifters have a lot of these.

Motor Units

• Type 1 (“slow twitch”):

  • Units with neurons innervating the slow efficient aerobic cells (maintaining posture, walking).

• Type 2 (“fast twitch”):

  • Units with the neurons innervating the large fibers that fatigue rapidly but develop large forces (jumping, weight lifting).

Regulation of Force

• Dependent on:

  • Rate of stimulation of individual motor units

  • The number or motor units recruited

Contraction

• Stimulus Single stimulus single twitch

• A single stimulus is delivered. The muscle contracts and relaxes

  1. Rate of stimulation

• Stimuli Partial relaxation Low stimulation frequency unfused (incomplete) tetanus

• If another stimulus is applied before the muscle relaxes completely, then more tension results. This is temporal (or wave) summation and results in unfused (or incomplete) tetanus.

• Stimuli" High stimulation frequency fused (complete) tetanus

• At higher stimulus frequencies, there is no relaxation at all between stimuli. This is fused (complete) tetanus.

• Increased frequency = Temporal Summation.

• A twitch lasts longer than an action potential!

• Tetanus results from Clostridium tetani infection

• Tetanus infection causes muscle tetanus and suppresses the inhibition of motor neuron activity

Recruitment

• Motor unit 1 Recruited (small fibers)

• Motor unit 2 recruited (medium fibers)

• Motor unit 3 recruited (large fibers)

• On more efficient fiber and then if corbic the big powerful needed Cancerbic)

• Ones v curbi U ↓ =more you recruit find stronger the contraction.

• As more units are recruited tension increases

• Usually, the most fatigue-resistant (small) motor units are recruited first