Neuromuscular transmission in Myasthenia Gravis
Basic, Organ-Based and Clinical Sciences
Myasthenia gravis is an autoimmune neuromuscular disease characterized by skeletal muscle weakness and fatigue. It results from IgG antibodies to the nicotinic acetylcholine receptor (AChR) which results in complement mediated destruction of acetylcholine receptors and membrane architecture at the neuromuscular junction. These effects on the post-junction motor end plate interfere with neuromuscular transmission.
Normal post junctional membrane architecture involves a complex network of synaptic folds and crests containing high concentrations of AChR’s in close proximity with sodium channels. The resting membrane of the motor end plate is -80mV. The binding of acetylcholine (ACh) to the AChR results in channel opening and cation influx. This creates a localized potential at the motor end plate which stimulates adjacent voltage gated sodium channel opening. When the membrane potential reaches a threshold level of -30mV, membrane depolarization and muscle contraction occur.
In myasthenia, neuromuscular transmission is interrupted at the post synaptic motor end plate. Autoimmune AChR destruction and motor endplate architectural disorganization limits ion influx and the post synaptic cell is unable to achieve the threshold membrane potential required for depolarization and muscle cell contraction. This manifests as weakness and easy fatigability of skeletal muscle.