NJN 6. Muscle Relaxation: Repolarization and Clinical Aspects

• These notes cover muscle relaxation, focusing on the repolarization phase and the roles of potassium and calcium.
• It also discusses clinical correlations like Myasthenia Gravis, Lambert-Eaton Syndrome, and the effects of various toxins and drugs on muscle function.

Relaxation Point

• Occurs at the peak of muscle contraction, around +30 mV on the voltage graph.
• Voltage-gated potassium channels open at this peak, leading to potassium ions moving out of the muscle cell due to their higher concentration inside.
• Potassium efflux contributes to the repolarization phase, decreasing the cell's positive charge and moving it towards its resting membrane potential (-90 mV).
• The peak potential also stimulates the inactivation gate of the potassium channel, causing it to slowly close and eventually block the channel at resting membrane potential.

Calcium's Role

• Calcium detaches from troponin as the muscle relaxes, signaling the sarcoplasmic reticulum to reclaim it.
• Troponin then allows tropomyosin to move back into its resting position, blocking the actin active sites and preventing myosin from binding.
• Calcium is transported back into the sarcoplasmic reticulum against its concentration gradient via two mechanisms:
  • Calcium ATPase pump: Uses ATP to transport calcium in and protons out.
  • Sodium-calcium exchanger: Uses the movement of sodium out of the sarcoplasmic reticulum to facilitate calcium entry (secondary active transport).

Repolarization

• Primarily due to potassium efflux, with calcium transport contributing a small amount.
• Inactivation gate of the potassium channel closes at resting membrane potential, preventing further potassium leakage.
• Once calcium leaves, troponin no longer pulls on tropomyosin, allowing the thin filaments to relax.
• The H zone reappears, the Z discs return to their normal position, and the I bands return to their normal size.

Clinical Correlations

Myasthenia Gravis

• Autoimmune disorder where antibodies attack nicotinic receptors on skeletal muscles, blocking acetylcholine binding.
• This prevents the generation of endplate potentials and action potentials, leading to muscle weakness and potential paralysis.

Lambert-Eaton Syndrome

• Autoimmune condition where antibodies block voltage-sensitive calcium channels, preventing calcium from entering and triggering the release of acetylcholine.
• Results in similar symptoms to Myasthenia Gravis, including progressive muscle weakness and potential respiratory failure.

Acetylcholinesterase

• Enzyme degrades acetylcholine into acetate and choline in the synapse, preventing continuous muscle stimulation.
• Acetylcholineesterase inhibitors like fisostigmine and neostigmine can be used to treat Myasthenia Gravis by increasing acetylcholine concentration and improving muscle contraction.
• Sarin is a nerve gas that irreversibly binds to acetylcholinesterase, leading to rapid acetylcholine buildup and potential respiratory paralysis.

Succinylcholine

• Drug used during general anesthesia to relax muscles.
• Acts as an agonist to acetylcholine, causing prolonged endplate potentials that eventually lead to the inactivation of sodium channels and muscle relaxation.

Toxins

• Botulinum toxin: Inhibits the fusion of synaptobrevin and syntaxin proteins, preventing acetylcholine release and causing muscle paralysis.
• Tetanus toxin: Inhibits the release of GABA from inhibitory neurons in the spinal cord, leading to muscle spasms and potential fractures.
• Dendrotoxin: Found in Black Mamba venom; inhibits voltage-gated potassium channels, causing increased calcium influx and convulsions. Alpha-bungarotoxin: Found in Cobra venom; blocks nicotinic receptors, preventing the generation of endplate potentials and causing paralysis.

Explore muscle relaxation with a focus on the repolarization phase, highlighting potassium and calcium's roles. Discusses clinical correlations such as Myasthenia Gravis and Lambert-Eaton Syndrome. Also covers the effects of toxins and drugs on muscle function during relaxation.