Electrophysiology of postsynaptic activation.

The safety factor for neuromuscular transmission depends upon the amount of ACh released from the nerve terminal, the number of AChRs, and the concentration of Na+ channels at the end plate potential. The postsynaptic end plate membrane of the neuromuscular junctions is specialized in three ways: (1) AChRs, Na+ channels, ChE, NOS, and other membrane-associated proteins are concentrated at the end plate; (2) the end plate cytoskeleton has a different composition of proteins as compared with extrajunctional membrane; and (3) the end plate membrane is mechanically different as compared with extrajunctional membrane. A blockade of neuromuscular transmission occurs when ACh release is inadequate or the end plate response to ACh is too small to trigger an AP. A safety factor for neuromuscular transmission exists because the EPP is larger than the threshold for generating an AP. The high concentration of Na+ channels at the end plate increases the safety factor for neuromuscular transmission by reducing the threshold depolarization required to initiate an AP. In MG, the safety factor is reduced due to loss of AChRs and loss of Na+ channels. The loss of AChRs reduces the EPP and the Na+ channel loss increases the threshold for triggering an AP.