MD137: Skeletal Muscle Function II

Skeletal Muscle: Structure & Function II

• MD137: Principles of Physiology lecture focusing on skeletal muscle contraction, excitation-contraction coupling, and the neuromuscular junction.
• Lecturer: Dr. K.McCullagh
• Course Description: This lesson covers the steps of electrical muscle activation, excitation-contraction coupling, neuromuscular junction details and clinical relevance.

The Neuromuscular Junction (NMJ)

• The neuromuscular junction (NMJ) is where the motor neuron synapses with skeletal muscle fibers.
• The NMJ is characterized by a motor axon, neuromuscular junctions and muscle fibers.
• The synaptic cleft is the gap between the axon terminal and muscle fiber.
• Synaptic vesicles release acetylcholine (ACh) into the synaptic cleft.
• Acetylcholine (ACh) receptors are integral proteins of the motor end plate
• Acetylcholine receptors bind ACh which opens ion channels, causing depolarization.

Excitation-Contraction Coupling

• This physiological mechanism connects electrical excitation to muscle contraction.
• An electrical signal at the muscle initiates chemical events releasing intracellular Ca²⁺, producing muscle action.
• The steps begin with the release of acetylcholine (ACh) from the motor neuron at the NMJ.
• ACh binds to receptors, allowing sodium (Na⁺) to enter the muscle fiber, generating an action potential.
• The action potential spreads along transverse tubules (T-tubules).
• The action potential triggers the release of calcium ions (Ca²⁺) from the sarcoplasmic reticulum (SR).
• Ca²⁺ binds to troponin, causing a conformational change in tropomyosin, exposing myosin-binding sites on actin.
• Myosin heads bind to actin, forming cross-bridges, and the muscle contracts through repeated cycles.
• Excitation-contraction coupling ends with the removal of calcium ions and resulting relaxation.

Neuromuscular Junctions and Motor End Plates

• Neuromuscular junction: The site where a motor neuron stimulates a muscle fiber.
• Motor end plate: The area of the muscle fiber sarcolemma where a motor neuron stimulates it.
• Structure: The motor end plate shows folded sarcolemma, mitochondria, synaptic vesicles and the neuromuscular cleft.
• Components: Nerve fiber branches, Muscle fiber nuclei, Myofibrils.

Clinical Implications

• Substances affecting acetylcholine transmission: Agents like botulinum toxin (Botox) and curare can alter muscle contraction.
• Botulism toxin (BOTOX): Used therapeutically in Focal Dystonias, Spasticity in cerebral palsy, and Cosmetic surgery. It inhibits acetylcholine release.
• Curare: A poison from South American plants that blocks acetylcholine receptors.
• Myasthenia gravis (MG): An autoimmune disease where the body attacks acetylcholine receptors.
• Treatment: Acetylcholinesterase inhibitors (e.g., neostigmine) and plasmapheresis can manage MG.

Electrical Activity at the Neuromuscular Junction

• Chemical transmitter release, inward membrane current, and generation of end-plate potentials (EPP) are essential components of neuromuscular junction function.
• Excitatory Postsynaptic Potentials (EPSP) play a role in triggering action potentials in the muscle fibre.

Sarcoplasmic Reticulum (SR)

• The SR is a modified endoplasmic reticulum that stores Ca²⁺ when the muscle is at rest.
• When the muscle fiber is stimulated, Ca²⁺ diffuses out of the SR via calcium release channels (ryanodine receptor; RyR).
• At the end of contraction, Ca²⁺ is actively pumped back into the SR via the Ca²⁺-ATPase pump.

Transverse Tubules (T-tubules)

• Narrow membranous tunnels.
• Formed by the sarcolemma, open to the extracellular environment.
• Able to conduct action potentials.

Excitation-Contraction Coupling (Detailed Steps)

• Action potential propagation along the sarcolemma and into T-tubules.
• Voltage-gated calcium channels (DHPR) in the T-tubules trigger the opening of calcium release channels in the SR (ryanodine receptors).
• Calcium release from SR into the sarcoplasm.
• Calcium binding to troponin, causing a conformational change that exposes myosin-binding sites on actin filaments.
• Myosin-actin cross-bridge cycling and muscle contraction.
• Calcium removal from the sarcoplasm and return to the SR, leading to muscle relaxation.

Explore the intricate mechanisms of skeletal muscle contraction, focusing on excitation-contraction coupling and the neuromuscular junction. This quiz delves into the processes involved in muscle activation and the role acetylcholine plays in muscle fiber communication. Perfect for students in physiology seeking to enhance their understanding of muscle dynamics.