Neuromuscular II

Neuromuscular System II

• The neuromuscular junction is a specialized synapse between a motor neuron and a muscle fiber.
• It occurs at the motor end plate, typically one per fiber.
• The synaptic cleft is 20-30nm wide and contains acetylcholinesterase (AChE).
• Subneural clefts increase the surface area of the postsynaptic membrane.
• Acetylcholine (ACh) is stored in small synaptic vesicles.
• ACh excites the muscle fiber membrane.
• The synaptic space contains large amounts of acetylcholinesterase which destroys ACh milliseconds after release.

Excitation of Skeletal Muscle

• Nerve impulses reach the terminal causing the release of acetylcholine into the synaptic cleft/space.
• Voltage-gated calcium channels allow calcium from the synaptic space to the inside of the nerve.
• Ca2+ activates Ca2+-Calmodulin dependent protein kinase which phosphorylates synapsin proteins.
• This frees ACh vesicles anchored to the cytoskeleton.
• ACh vesicles move, dock at release sites, fuse, and release ACh into the synaptic space (exocytosis).
• ACh attaches to the alpha subunits of acetylcholine receptors.
• Acetylcholinesterase degrades ACh into acetate and choline which is reabsorbed into the terminal for re-use.
• Acetylcholinesterase mostly lines the connective tissue in the synaptic space, though a small amount might be free in the space.
• These acetylcholine-gated ion channels are near the openings of the subneural clefts, comprised of 5 transmembrane protein subunits.
• Two ACh molecules attach to the alpha subunits to open the channel allowing Na+, K+, and Ca2+ ions (cations) to flow inward (especially Na+) while repelling anions.
• The resulting positive potential change (end plate potential) causes adjacent voltage-gated sodium channels to open, triggering greater Na+ influx. This propagates 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 sodium channels to open to create a positive feedback loop, opening more sodium channels, causing an action potential.

Muscle Fiber Contraction: Excitation-Contraction Coupling

• Action potentials (APs) start in the brain.
• APs arrive at axon terminals, releasing acetylcholine (ACh).
• ACh crosses the synapse and binds to ACh receptors on the plasmalemma.
• Na+ pours into the muscle fiber.
• The local area potential in the muscle increases.
• Voltage-gated Na+ channels open.
• APs travel down the plasmalemma and T-tubules.
• Ca2+ is released from the sarcoplasmic reticulum (SR).

Transverse Tubules and Excitation-Contraction Coupling

• Transverse Tubules (T tubules) transmit APs from the surface of muscle fibers deep to the level of the myofibrils.
• They run transverse to the myofibrils, starting at the cell membrane and penetrating all the way from one side of the muscle fiber to the other.
• AP travels along T tubules and near the sarcoplasmic reticulum (SR) .
• AP allows Ca2+ release from the SR.
• The influx of Ca2+ allows muscle contraction.

Role of Ca2+ in Muscle Contraction

• AP arrives at the SR from the T-tubule.
• SR is sensitive to electrical charge.
• Causes mass release of Ca2+ into the sarcoplasm.
• Ca2+ binds to troponin on the thin filament.
• Tropomyosin covers the myosin-binding site, blocking actin-myosin attraction.
• Troponin-Ca2+ complex moves, exposing actin-binding sites on actin.
• Myosin binds to actin and contraction occurs.

Excitation-Contraction Coupling

• Nerve impulse travels down T tubules and causes release of Ca2+ from the sarcoplasmic reticulum (SR).
• Ca2+ binds to troponin and causes a positional change in tropomyosin, exposing active sites on actin.
• This allows strong binding between actin and myosin, causing contraction to occur.

Contraction

• At rest, myosin cross-bridges occur in a weak binding state.
• Ca2+ binds to troponin, causing a shift in tropomyosin to uncover active sites, forming a strong binding state.
• P1 is released from myosin, resulting in cross-bridge movement.
• ADP is released from myosin.
• ATP attaches to myosin, breaking the cross-bridge and forming a weak binding state. ATP is broken down to ADP & P1, energizing the myosin.
• This cycle continues as long as Ca2+ and ATP are available

Muscle Relaxation

• AP ends, halting electrical stimulation of the SR.
• Ca2+ is pumped back into the SR, stored until the next AP arrives.
• Requires ATP.
• Called the SR calcium ATPase pump.
• Without Ca2+, troponin and tropomyosin return to their resting conformation.
• Myosin-binding sites are covered, preventing actin-myosin cross-bridging.

SR Calcium ATPase Pump

• Two isoforms found in adults: SERCA1 and SERCA2a.
• SERCA2a is found in Type I, cardiac, and smooth muscle.
• The ability to release and re-sequester Ca2+ plays a role in exercise-induced fatigue. Studies show that training programs with all-out sprints affect the amount of SERCA isoforms and can improve recovery and ability to repeat the activity.

Factors Influencing Force Generation

• Neural factors: orderly recruitment, rate coding, and synchronization.
• Contractile factors: skeletal muscle size, architecture, length-tension relationship, contractile speed, and history.

Motor Units

• α-motor neurons innervate muscle fibers.
• A motor unit is a single α-motor neuron and all the fibers it innervates.
• More operating motor units = more contractile force.
• The finer the control required, the fewer the number of fibers innervated by a motor unit.
• Motor units overlap for better coordination.
• Not a strong relationship between fiber type and motor unit size.
• Small units (e.g., larynx, extraocular) have 10 fibers/motor unit, and have rapid control, while large units (e.g., quadriceps) have 1000 fibers/motor unit and have slower, coarse control.

Motor Unit Properties

• Fast fatigable (FF: type 2x): fast twitch, high fatigue rate.
• Fast fatigue-resistant (FR: type lla): fast twitch, moderate fatigue rate.
• Slow (S: type 1): slow twitch, low fatigue rate

Motor Unit Recruitment

• The process of adding motor units to increase force.
• Size principle: motor neurons with progressively larger axons are recruited as muscle force increases.
• Selective recruitment and firing pattern of fast-twitch and slow-twitch motor units controls movement by producing a coordinated response.

Muscle Fiber Types

• Most muscles contain both fast and slow fibers in different proportions depending on function.
• Fiber types in a motor unit are all the same type (fast or slow).
• Slow fibers (Type I): oxidative, small diameter, high myoglobin content, high capillary density, many mitochondria, and low glycolytic enzyme content.
• Fast fibers (Type II): glycolytic, large diameter, low myoglobin content, low capillary density, few mitochondria, and high glycolytic enzyme content.

Fiber Type Determinants

• Histochemistry can differentiate fast and slow muscle fibers.
• Motor units containing slow fibers are recruited first for normal contractions, while fast fibers are used for forceful contractions.
• Genetic and training factors influence fiber type proportions.
• Endurance training may lead to some (10%) changes in fiber type proportions but not complete changes.
• Aging can cause loss of type II motor units.

This quiz covers key concepts regarding action potentials in muscle fibers, including the initiation processes, the effects of end plate potentials, and the role of acetylcholine in excitation. Test your understanding of how muscle fibers respond to electrical signals and the subsequent changes in membrane potential.