Neuromuscular Transmission and Muscle Contraction

Motor Units

• Definition: A motor unit is composed of a motor neuron and the skeletal muscle fibers it innervates.
• Composition: Each motor neuron innervates multiple muscle fibers.
• Action Potential: When an action potential occurs in the motor neuron, all muscle fibers in the unit contract.
• Example: A motor neuron supplying five muscle fibers – all fibers contract when the neuron is stimulated.
• Variation: Different motor units supply different numbers of muscle fibers. E.g., large muscles (back) vs. small muscles (hand, eye).

Recruitment of Motor Units

• Increase in muscle contraction force is achieved by recruiting multiple motor units.
• Recruitment starts with smaller units and progresses to larger ones for greater tension.

Neuromuscular Junction (NMJ)

• Components: Consists of nerve endings, vesicles (containing acetylcholine), Schwann cells, synaptic cleft, and acetylcholine receptors.
• Process:
  1. Action potential arrives at the motor neuron end.
  2. Calcium channels open, and calcium enters the neuron.
  3. SNARE proteins facilitate exocytosis, releasing acetylcholine.
  4. Acetylcholine binds to receptors, opening ligand-gated sodium channels.
  5. If the threshold potential is reached, voltage-gated sodium channels open, initiating an action potential in the muscle fiber.
• Neurotransmitter: Acetylcholine.
• Motor End Plate: The area where the nerve meets the muscle fiber at the NMJ.
• Enzyme: Acetylcholine esterase breaks down acetylcholine to stop transmission.

Disruptions of Neuromuscular Signaling

• Curare: Binds to acetylcholine receptors, preventing muscle contraction; not broken down by acetylcholine esterase.
• Organophosphates: Inhibit acetylcholine esterase, leading to excessive contraction. Antidote: Pralidoxime (prevents action of nerve gas) and Atropine (blocks receptors).
• Succinylcholine: Binds to cholinergic receptors with higher affinity than acetylcholine; used to induce muscle paralysis during surgery.
• Clostridium botulinum toxin (Botox): Blocks acetylcholine release, used in cosmetic treatments and to treat other conditions.

Muscle Contraction Mechanism

• Sliding Filament Model:
  1. Myosin heads bind to actin forming a cross-bridge.
  2. Unbinding requires ATP.
  3. ATP is hydrolyzed to ADP and phosphate, “cocking” myosin heads for the next cycle.
  4. Calcium binds to troponin, moving tropomyosin and exposing binding sites on actin.
• Calcium Role: Stored in the sarcoplasmic reticulum, released upon action potential.
  • Voltage-gated calcium channels with DHP and ryanodine receptors release calcium.
  • Calcium pump (Calcium ATPase) actively sucks back calcium for muscle relaxation.

ATP Requirement in Muscle Contraction

• Uses of ATP:
  • Sodium-potassium ATPase pump in plasma membrane for action potential.
  • Calcium ATPase pump in sarcoplasmic reticulum to reabsorb calcium.
  • Myosin heads for cross-bridge cycling and force generation.
  • Releasing myosin from actin.

Summary

• Understand the structure and function of motor units and neuromuscular junctions.
• Recognize how different factors influence muscle contraction and relaxation.
• Identify how ATP and calcium are crucial for muscle function.
• Be aware of various disruptions to neuromuscular signaling and their implications.

For further reading or questions, please refer to the lecture materials or contact me.