Skeletal Muscle: Structure & Function II

Skeletal Muscle: Structure & Function II

• Lecture: MD137: Principles of Physiology, Dr. K.McCullagh, 2024
• Topic: Electrical activation of muscle contraction, excitation-contraction coupling, neuromuscular junction, and clinical relevance.

Neuromuscular Junction (NMJ)

• Location: The site where a motor neuron stimulates a muscle fiber.
• Structure: Image shows somatic motor neuron axon and skeletal muscle fibers connected by many neuromuscular junctions (NMJs).

Excitation-Contraction Coupling

• Mechanism: A physiological process where an electrical discharge at the muscle initiates chemical events at the cell surface. This releases intracellular Ca²⁺, producing muscle action.

Excitation-Contraction Coupling Steps

• Step 1: Acetylcholine (ACh) is released from the somatic motor neuron.
• Step 2: ACh binds to nicotinic ACh receptors, causing ligand-gated channels to open.
• Step 3: Sodium (Na⁺) diffuses inwards, creating a depolarizing stimulus.
• Step 4: An action potential is produced.
• Step 5: The action potential travels along transverse tubules (T-tubules).
• Step 6: Voltage-gated calcium (Ca²⁺) channels open.
• Step 7: Ca²⁺ is released from the sarcoplasmic reticulum (SR).
• 8: Ca²⁺ binds to troponin, causing a shift in tropomyosin, exposing myosin-binding sites on actin filaments.
• Step 9: Cross-bridges form between actin and myosin.
• Step 10: Myosin heads rotate and generate force.
• Step 11: Muscle contraction ensues.

Neuromuscular Junctions & Motor End Plates

• Motor end plate: The area of the muscle fiber sarcolemma where a motor neuron stimulates it.
• Components: Parts like motor neuron axon, muscle fiber nucleus, nerve fiber branches, synaptic vesicles and synaptic cleft are features of this structure.

The Neuromuscular Junction (Detailed)

• Step 1: Motor neuron action potential arrives.
• Step 2: Calcium (Ca²⁺) enters the axon terminal.
• Step 3: Acetylcholine (ACh) vesicles fuse with the membrane and release ACh into the synaptic cleft.
• Step 4: ACh binds to receptors on the motor end plate, opening ion channels.
• Step 5: Sodium (Na⁺) enters the muscle fiber, generating an end-plate potential (EPP).
• Step 6: The EPP initiates an action potential in the muscle fiber.
• Step 7: Muscle fiber action potential travels along the sarcolemma and into T-tubules.
• Step 8: Depolarization of the T-tubules triggers release of Ca²⁺ from the sarcoplasmic reticulum.
• Step 9: Ca²⁺ initiates the contraction.

Structural Features of the Neuromuscular Junction

• Components: Schwann cell, synaptic vesicles, synaptic cleft, postjunctional fold, and nicotinic acetylcholine receptors (on the postjunctional membrane) are parts of NMJ.

Electrical Activity at the Neuromuscular Junction

• Chemical transmitter release: Neurotransmitter (ACh) is released at nerve terminal, triggering signal.
• Inward membrane current: This current flows into motor end plate.
• End plate potential (EPP): Produced by inward current, it's a depolarization.

Electrical Activity at the Neuromuscular Junction (cont.)

• Many motor axon action potentials: This produces an EPP that can trigger muscle contraction.
• Na⁺ channel threshold: Action potential occurs when the EPP depolarization surpasses the Na+ channel threshold.

Clinical Implications

• Substance affecting ACh transmission: Impacts muscle contraction.
• Botulinum toxin (Botox): Used for various conditions (dystonias, cerebral palsy). It inhibits ACh release.
• Curare: A poison arrow toxin blocking ACh receptors.
• Acetylcholinesterase inhibitors: Used for myasthenia gravis (e.g., neostigmine) to increase available ACh.

Myasthenia Gravis

• Autoimmune disease: The immune system attacks ACh receptors at the neuromuscular junction.
• Symptoms: Muscle weakness (e.g., eye and limb muscles).
• Incidence: Approximately 1 in 5000 people.
• Treatment: Acetylcholinesterase inhibitors, plasmapheresis.

Acetylcholinesterase Inhibitors

• Mechanism: Prevents breakdown of ACh in the synaptic cleft. Increases ACh levels which compensates for the low numbers of ACh receptors in myasthenia gravis.
• Example: Neostigmine

Stimulating a Muscle Contraction

• Acetylcholine release: From the motor neuron.
• End plate potentials: Produced at the motor end plate.
• Action potentials: Generated in the muscle.
• Calcium release: Voltage gated calcium channels (DHPRs)in Transverse tubules change shape triggering sarcoplasmic reticulum channels to open.
• Cross-bridge cycling: Binding, rotating and generating force, using ATP.

Muscle Relaxation

• Action potentials cease: Electrical signals stop.
• Calcium reuptake: Ca²+ is pumped back into SR by Ca²+ -ATPase pump..
• Cross-bridge release: No more Ca²⁺ is available to bind to troponin C, so cross-bridges detach.

Excitation-Contraction Coupling (Summary)

• Sequence of events: Depolarization, calcium release, cross-bridge formation, rotation, and force creation.
• Temporal relationship: Action potential precedes Ca²⁺ increase, which precedes contractile force generation.

Sarcoplasmic Reticulum (SR)

• Function: Stores Ca²⁺ when muscle is at rest
• Calcium release: SR releases Ca²⁺ when muscle is stimulated.
• Mechanism: This release is via RyR (ryanodine receptors).
• Calcium reuptake: Ca²⁺ is actively pumped back into SR by sarcoplasmic reticulum (SR) Ca²⁺-ATPase pumps.

Transverse Tubules (T-tubules)

• Structure: Membrane tunnels from sarcolemma. Have access to extracellular environment.
• Function: Conduct action potentials deep within the muscle fiber.

Myofibrils and Sarcoplasmic Reticulum (SR)

• Structures: Components involved in muscular contraction.
• Relationship: Myofibrils are composed of filaments and related to the sarcoplasmic reticulum (SR) which is modified endoplasmic reticulum.

Dihydropyridine Receptor (DHP)

• Integral membrane protein: Present in the transverse tubules (T-tubules) of muscle cells.
• Coupling mechanism: DHP receptor contributes to the excitation-contraction coupling, which is the process that links muscle excitation to contraction.
• Related components: DHP receptors interact with ryanodine receptors.

Ca²⁺-ATPase Pump

• Function: Pumps Ca²⁺ back into the sarcoplasmic reticulum (SR) after contraction.
• ATP requirement: This process uses a significant amount of ATP to maintain calcium levels.
• Regulation: Actively regulates calcium levels, ensuring muscle relaxation.

Explore the intricate details of skeletal muscle structure and function in this quiz. Covering the neuromuscular junction and the process of excitation-contraction coupling, this quiz will challenge your understanding of muscle physiology. Relevant for MD137 Principles of Physiology, it tests your knowledge on muscle activation and its clinical relevance.