5410 1.4

Muscle Physiology: Fundamentals 1.4

A. Contraction of Skeletal Muscle

Three Kinds of Muscle

• Skeletal Muscle: Striated and voluntary. Controls movement of the skeleton.
• Cardiac Muscle: Striated and involuntary. Found in the heart.
• Smooth Muscle: Involuntary. Found in the walls of internal organs.

Skeletal Muscle Cell Excitability

• Neurons generate signals via action potentials.
• Muscle cells are capable of responding to these signals by contracting.

Neuromuscular Junction (NMJ)

• A synapse between a motor neuron and a skeletal muscle cell.
• There is typically one neuromuscular junction per skeletal muscle cell.
• A single motor neuron can innervate several muscle cells.
• Motor Unit: Consists of a single motor neuron and all the muscle fibers it innervates.
• The neurotransmitter released at the NMJ is acetylcholine (ACh).

Overview of Muscle Contraction

1. A motor neuron is stimulated.
2. An action potential (AP) travels to the neuromuscular junction.
3. ACh is released from the terminal bouton (axon terminal) of the motor neuron.
4. ACh binds to postsynaptic receptors on the skeletal muscle cell.
5. The skeletal muscle depolarizes.
6. When the depolarization reaches the threshold, the muscle cell contracts.

Muscle Cell Structure

• Muscle Fiber / Muscle Cell / Myocyte: Interchangeable terms for a single muscle cell.
• Myofibrils: Several per muscle cell, composed of repeating contractile units.
• Sarcomere: The fundamental contractile unit of striated muscle, composed of actin and myosin filaments.
• Myosin: The thick filament.
• Actin: The thin filament.
• Bands: I band, A band, H zone (regions within the sarcomere based on filament overlap).
• Lines: Z line (defines sarcomere boundaries), M line (center of the A band).

Actin (Thin Filament)

• Tropomyosin: A protein that lies in the groove of the actin helix, blocking its binding sites for myosin in a relaxed state.
• Troponin: Anchored to tropomyosin, it provides a binding site for calcium ions ($Ca^{2+}$).

Myosin (Thick Filament)

• Myosin Head: Has several critical functions:
  • Binds to actin.
  • Binds to ATP.
  • Hydrolyzes ATP to release energy, which powers the contraction cycle.
• The myosin tail is connected to the head by a hinge region, allowing movement.

Sarcoplasmic Reticulum (SR)

• A system of membranous tubes within the muscle cell that sequesters $\text{Ca}^{2+}$ away from the actin and myosin.
• $Ca^{2+}$ is absolutely required for muscle contraction.
• If $\text{Ca}^{2+}$ were freely available in the sarcoplasm, the muscle cell would never be able to relax.

Mitochondria

• Abundant in muscle cells to provide a continuous supply of energy in the form of ATP (adenosine triphosphate) for muscle contraction and relaxation.

Mechanism of Skeletal Muscle Contraction (Detailed)

1. A motor nerve action potential reaches the axon terminal of the motor neuron.
2. Acetylcholine (ACh) is released from the presynaptic neuron into the synaptic cleft.
3. ACh travels across the synaptic cleft and activates receptors on the postsynaptic membrane (sarcolemma) of the muscle cell.
4. ACh receptors trigger a depolarization of the muscle cell membrane, leading to an action potential in the muscle cell.

Muscle Cell Action Potential ($\text{AP}$) and $\text{Ca}^{2+}$ Release

• The AP in the muscle cell travels along the sarcolemma (muscle cell membrane).
• Transverse or T-tubules: These are deep infoldings of the sarcolemma that extend into the muscle cell. They quickly bring the AP into close contact with the sarcoplasmic reticulum (SR).
• The SR contains high concentrations of $\text{Ca}^{2+}$. When the AP reaches the SR via the T-tubules, it causes the SR to open $\text{Ca}^{2+}$ channels, releasing $\text{Ca}^{2+}$ into the sarcoplasm (cytoplasm of a muscle cell).
• The released $\text{Ca}^{2+}$ then comes into contact with the myofibrils.

Role of $\text{Ca}^{2+}$ in Muscle Contraction

• At rest, the binding sites on actin for myosin are blocked by tropomyosin, preventing actin and myosin from binding.
• Troponin has a specific binding site for $\text{Ca}^{2+}$.
• When $\text{Ca}^{2+}$ binds to troponin, it causes a conformational change that rolls the tropomyosin away, exposing the actin/myosin binding sites.

Actin + Myosin Crossbridge Cycle

1. An action potential arrives at the muscle cell, eventually leading to $\text{Ca}^{2+}$ release from the SR.
2. $Ca^{2+}$ binds to troponin C.
3. The actin binding site is exposed.
4. Myosin binds to actin, forming a crossbridge.
5. The myosin head pulls the actin filament in what is called the "powerstroke." This action immediately causes the release of ADP and inorganic phosphate ($\text{P}_{i}$) from the myosin head.

Myosin/ATP Interaction and Sliding Filament Theory

• ATP binds to the myosin head.
• Myosin cleaves (hydrolyzes) the ATP into ADP and $\text{P}_{i}$.
• The energy released from ATP hydrolysis "cocks" the myosin head, storing energy in preparation for the next cycle of actin binding.
• This process allows the sliding filament theory of muscle contraction, where the thin filaments slide past the thick filaments, shortening the sarcomere.
• If $\text{Ca}^{2+}$ is still present, the cycle will repeat, leading to continued contraction.

Reuptake of $\text{Ca}^{2+}$ and Relaxation

• After the action potential passes and neural stimulation ceases, $\text{Ca}^{2+}$ pumps (SERCA pumps) in the sarcoplasmic reticulum actively remove $\text{Ca}^{2+}$ from the sarcoplasm, returning it to the SR.
• As $\text{Ca}^{2+}$ concentration in the sarcoplasm decreases, troponin is no longer $\text{Ca}^{2+}$-bound.
• Tropomyosin returns to its resting position, blocking the actin binding sites.
• Myosin can no longer bind to actin, and the muscle relaxes.

How Muscle Contraction Force Changes (Physiology Affects Function)

• Action potentials are "all or nothing"; once threshold is reached, a full AP occurs.
• Each crossbridge cycle between actin and myosin has a similar strength and degree of shortening.
• The force of muscle contraction can be varied by:
  1. Sarcomere length at the beginning of contraction: Muscle generates less power if it is overstretched or over-contracted from its optimal resting length.
  2. Summation: The force is determined by the motor neuron firing rate:
     • Temporal Summation: Multiple action potentials arriving in a short amount of time cause successive contractions to add up, increasing force.
     • Spatial Summation: Activation of multiple motor neurons simultaneously generates a greater total force.

Characteristics of Muscle Contraction

• Isometric vs. Isotonic Contraction:
  • Isometric Contraction: Muscle contracts and generates tension but does not visibly shorten or lengthen (e.g., holding a heavy weight stationary). High tension, no movement.
  • Isotonic Contraction: Muscle contracts and changes length while maintaining relatively constant tension (e.g., lifting