Neuromuscular System II

Neuromuscular System II

• This presentation covers the neuromuscular junction, excitation-contraction coupling, factors influencing force generation, motor unit function, and muscle fiber types within the context of applied physiology.

Objectives

• Discuss the neuromuscular junction
• Describe excitation-contraction coupling
• Describe factors influencing force generation
• Describe how motor units function
• Identify characteristics of different muscle fiber types

The Neuromuscular Junction

• A specialized synapse between a motoneuron and a muscle fiber.
• Occurs at the motor end plate (usually only one per fiber).
• Includes myelinated sheath, axon, terminal nerve branches, and teloglial cell.

Synaptic Cleft

• 20-30 nm wide
• Contains large quantities of acetylcholinesterase (AChE)

Subneural Clefts

• Increases the surface area of the postsynaptic membrane.
• Contains acetylcholine-gated channels at the tops and voltage-gated Na+ channels at the bottom half.

Excitation of Skeletal Muscle: Neuromuscular Transmission

• Mitochondria are essential for energy requirements for acetylcholine synthesis, which is then packaged into synaptic vesicles.
• Acetylcholine molecules are densely packed in synaptic vesicles (approximately 10,000 per vesicle).

Neuromuscular Junction (Continued)

• Acetylcholine (ACh) is stored in small synaptic vesicles.
• ACh excites the muscle fiber membrane.
• The synaptic space contains acetylcholinesterase, which destroys acetylcholine a few milliseconds after release.
• Contains dense bar, calcium channels, basal lamina, and acetylcholinesterase.

Excitation of Skeletal Muscle: Neuromuscular Transmission (Continued)

• Nerve impulses to the terminal result in ACh release into synaptic cleft.
• ACh attaches to alpha subunits of acetylcholine receptors.
• ACh is degraded to acetate and choline (actively reabsorbed).
• Acetylcholinesterase lines connective tissue in the space.

Neuromuscular Transmission (Continued)

• Acetylcholine receptors are near the openings of subneural clefts.
• These comprised of five transmembrane protein subunits.
• A conformational change occurs when two ACh molecules attach to alpha subunits.
• The resulting local positive potential change (end-plate potential) can trigger adjacent voltage-gated sodium channels.
• Triggers the propagation of an action potential along the muscle membrane, leading to contraction.

End Plate Potential to Muscle Fiber Excitation

• Some end-plate potentials are strong enough to cause enough sodium channels to open to start a positive feedback loop.
• Eventually causes an action potential.

Muscle Fiber Contraction: Excitation-Contraction Coupling

• Action potential starts in the brain.
• Action potential arrives at axon terminal, releasing acetylcholine (ACh).
• ACh binds to ACh receptors.
• Sodium (Na+) pours into the muscle fiber membrane.
• Increasing potential in muscle and opening voltage gated Na+ channels.
• Action Potential travels down plasmalemma and T-tubules.
• Triggers calcium (Ca2+) release from sarcoplasmic reticulum (SR).

Transverse Tubules and Excitation-Contraction Coupling

• Transverse Tubules (T tubules) transmit Action Potentials (APs) from the surface of muscle fibers to the myofibrils.
• Run transverse to the myofibrils.
• Start at the cell membrane and penetrate the entire muscle fiber.
• Function in excitation-contraction coupling.
• AP travels along T-tubules near the sarcoplasmic reticulum.

Role of Ca2+ in Muscle Contraction

• AP arrives at SR from T-tubules.
• Release of Ca2+ into the sarcoplasm caused by electrical charge.
• Ca2+ binds to troponin on thin filaments.
• Changes the position of tropomyosin to expose myosin-binding sites on actin.
• Myosin binds to actin and contraction occurs.

Excitation-Contraction Coupling (Continued)

• Depolarization of motor end plate.
• Nerve impulse travels along T-tubules.
• Ca++ release from SR.
• Causes a change in tropomyosin position revealing active sites on actin.

Contraction

• Myosin cross-bridges bound weakly at rest.
• Ca2+ binding to troponin shifts tropomyosin.
• Cross-bridges form, and stronger binding state occurs.
• Phosphate (P₁) is released from myosin.
• Cross-bridge movement.
• ATP binds to myosin.
• Breaking cross-bridges and forming weak binding state.
• ATP is hydrolyzed to energize myosin for the next cycle.
• This cycle repeats until Ca2+ levels fall.

Muscle Relaxation

• AP ends, electrical stimulation of SR stops.
• Ca2+ is pumped back into SR (requiring ATP).
• Troponin and tropomyosin return to resting confirmation.
• Myosin-binding site is covered.

SR Calcium ATPase pump

• Two isoforms, SERCA 1 and SERCA 2.
• SERCA 2 is found mostly in type II muscle fibers, cardiac, and smooth muscle.
• Capacity to release and re-sequester Ca2+ is a factor in fatigue.

Factors Influencing Force Generation

• Neural factors: Orderly recruitment, Rate coding, Synchronization.
• Contractile factors: Skeletal muscle size, Skeletal muscle architecture, Length-tension relationship, Contractile speed, Contractile history.

Rate Coding

• The rate at which motor units discharge action potentials. The higher the rate, the greater the strength of muscle contraction.

Length-tension Relationship

• Relationship between the length of the sarcomere and the tension it can produce. The graph shows ideal length for muscle tension.

Contraction Speed

• Speed at which a muscle contracts and relaxes.

Motor Units

• α-Motor neurons innervate muscle fibers.
• Single α-motor neuron + all innervated fibers = motor unit
• More operating motor units = increased contractile force.
• Precision of control is determined by the number of fibers in a motor unit

Motor Units (Continued)

• Small motor units (e.g., larynx, extraocular) control fine movements with few fibers/unit.
• Large motor units (e.g., quadriceps) control coarse movements with many fibers/unit.
• Motor units overlap and provide coordination.

Motor Unit Properties

• Three types of motor units: slow-oxidative, fast-oxidative, fast-glycolytic.
• Properties include twitch rate, rate of fatigue, and associated fiber type.

Motor Unit Recruitment

• Process of adding motor units to increase force.
• Size principle: Larger motor neurons with progressively larger axons are recruited as further force is required.
• Selective recruitment: Fast-twitch and slow-twitch motor units are recruited in a selective manner based on the needed force.

Muscle Fiber Types

• Most muscles contain both types (oxidative and glycolytic).
• Proportions can differ.
• Fibers in a motor unit are of the same type.
• Fast and slow fibers have different fatigue resistance.

Muscle Fiber Type Properties

• Biochemical properties: Oxidative capacity, Type of ATPase
• Contractile properties: Maximal force, Speed of contraction, Muscle fibre efficiency.

Characteristics of Muscle Fiber Types

• Slow twitch (Type I): Small diameter, high myoglobin, high capillary density.
• Fast twitch (Type II): Large diameter, low myoglobin, low capillary density.

Fiber Type Determinants

• Multiple factors affect fiber type: genetic, training, and aging.