MD137: Skeletal Muscle Function II Quiz

Skeletal Muscle: Structure & Function II

• MD137: Principles of Physiology lecture covers the steps of electrical activation of muscle contraction, excitation-contraction coupling, and the neuromuscular junction. Clinical relevance is also discussed.

The Neuromuscular Junction (NMJ)

• The NMJ is where a motor neuron stimulates a muscle fiber.
• This area shows somatic motor neuron axon and skeletal muscle fibers with neuromuscular junctions (NMJs)

Excitation-Contraction Coupling

• A physiological mechanism where an electrical discharge at the muscle initiates chemical events that release intracellular Ca²⁺ and cause muscle action.

Steps of Excitation-Contraction Coupling

• Neurotransmitter Release: Acetylcholine (ACh) is released from the somatic motor neuron.
• ACh Binding: ACh binds to nicotinic ACh receptors, opening ligand-gated channels.
• Sodium Influx: Sodium (Na⁺) diffuses into the muscle fiber, creating a depolarizing stimulus.
• Action Potential Generation: An action potential is produced.
• Action Potential Propagation: Action potentials are conducted along the transverse tubules (T-tubules).
• Calcium Release: Action potentials open voltage-gated calcium (Ca²⁺) channels. Ca²⁺ is released from the sarcoplasmic reticulum (SR).
• Calcium Binding: Ca²⁺ binds to troponin, allowing actin-myosin cross-bridges to form.
• Muscle Contraction: Cross-bridges bind, rotate, and generate force.
• Calcium Removal: Ca²⁺ is actively pumped back into the sarcoplasmic reticulum (SR) by the Ca²⁺-ATPase pump.
• Muscle Relaxation: No more Ca²⁺ is available, so the muscle fiber relaxes.

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's sarcolemma where a motor neuron stimulates it.

The Neuromuscular Junction (Detailed)

• Motor neuron action potential: Initiates the process.
• Calcium entry: Calcium enters voltage-gated channels.
• Acetylcholine release: Acetylcholine is released into the synaptic cleft.
• Acetylcholine binding: Acetylcholine binds to receptors on the muscle fiber.
• Sodium entry: Sodium enters, generating an action potential.
• Muscle action potential: Propagated along the muscle fiber's membrane.
• Calcium release: Calcium is released from the sarcoplasmic reticulum.
• Muscle contraction: Calcium binding triggers muscle contraction.
• Acetylcholine degradation: Acetylcholinesterase breaks down acetylcholine.

Structural Features of the Neuromuscular Junction

• Schwann cell: Encloses and isolates the axon terminal.
• Synaptic vesicles: Contain acetylcholine (ACh).
• Synaptic cleft: The gap between the neuron and muscle fiber.
• Postjunctional fold: Increases the surface area of the muscle fiber membrane.
• Nicotinic acetylcholine receptors: Molecules that bind to ACh.

Electrical Activity at the Neuromuscular Junction

• Chemical transmitter release: Motor axon action potential triggers release of acetylcholine into the synaptic cleft
• Inward membrane current: Acetylcholine binding leads to sodium ion inward current, generating an excitatory postsynaptic potential (EPSP).
• Depolarization below threshold: EPSP not strong enough to trigger a full action potential.

Electrical Activity at the Neuromuscular Junction (Continued)

• Many motor axon action potentials: Repeated signals create numerous EPSPs, each summating to reach the action potential threshold.
• Na⁺ channel threshold: Action potential is triggered when sodium channels open above a critical threshold.

Clinical Implications

• Substances affecting acetylcholine transmission affect muscle contraction.
• Botulism toxin (Botox) inhibits acetylcholine release, used for various medical conditions.
• Curare blocks acetylcholine receptors, found in poison arrows.
• Acetylcholinesterase inhibitors treat myasthenia gravis (muscle weakness due to insufficient acetylcholine).

Myasthenia Gravis (Grave Muscle Weakness)

• An autoimmune disease where the immune system attacks acetylcholine receptors at the neuromuscular junction.
• Incidence: 1 in 5000 people.
• Treatment: Acetylcholinesterase inhibitors (e.g., neostigmine) and plasmapheresis (plasma exchange).

Acetylcholinesterase Inhibitors

• Inhibition mechanism: Prevents breakdown of acetylcholine (ACh).
• Result: High ACh concentration in synaptic cleft, compensating for reduced receptor numbers.

Excitation-Contraction Coupling (Summary)

• Begins with an action potential.
• Leads to calcium release.
• Cross-bridging and muscle contraction are activated.
• Relaxation occurs through calcium reabsorption.

Transverse Tubules

• Narrow membranous tunnels from sarcolemma.
• Open to extracellular environment.
• Conducts action potentials.

Sarcoplasmic Reticulum (SR)

• Stores Ca²⁺ when muscle is at rest.
• Releases Ca²⁺ through RyR (ryanodine receptor) channels when stimulated.
• Actively pumps Ca²⁺ back into the SR during relaxation.

Myofibrils and Sarcoplasmic Reticulum

• Myofibrils contain actin and myosin filaments, involved in muscle contraction.
• SR surrounds the myofibrils.
• Structures are visualized in the provided image.

Temporal Sequence of Events

• Action potential precedes the increase in intracellular calcium (Ca²⁺).
• Calcium increase precedes cross-bridge cycling and force generation.

Stimulating a Muscle Contraction

• Acetylcholine is released .
• End-plate potentials (EPPs) are created.
• Action potentials are generated.
• Ca2+ channels in transverse tubules (T-tubules) are opened by the altered shape of DHPRs on the T-tubules
• Ca2+ release from sarcoplasmic reticulum (SR)

Muscle Relaxation

• Action potentials stop.
• Ca²⁺-ATPase pumps Ca²⁺ back into the SR.
• No more calcium is available for cross-bridge attachment

Test your knowledge on the structure and function of skeletal muscle, focusing on electrical activation and excitation-contraction coupling. This quiz covers the neuromuscular junction and its clinical relevance, highlighting key processes involved in muscle contraction.