Abstract
Myasthenia gravis (MG), the most common of autoimmune myasthenic syndromes, is characterized by antibodies directed against the skeletal muscle acetylcholine receptors (AChRs). Endplate Na(+) channels ensure the efficiency of neuromuscular transmission by reducing the threshold depolarization needed to trigger an action potential. Postsynaptic AChRs and voltage-gated Na(+) channels are both lost from the neuromuscular junction in MG. This study examined the impact of postsynaptic voltage-gated Na(+) channel loss on the safety factor for neuromuscular transmission. In intercostal nerve-muscle preparations from MG patients, we found that endplate AChR loss decreases the size of the endplate potential, and endplate Na(+) channel loss increases the threshold depolarization needed to produce a muscle action potential. To evaluate whether AChR-specific antibody impairs the function of Na(+) channels, we tested omohyoid nerve-muscle preparations from rats injected with monoclonal myasthenogenic IgG (passive transfer model of MG [PTMG]). The AChR antibody that produces PTMG did not alter the function of Na(+) channels. We conclude that loss of endplate Na(+) channels in MG is due to complement-mediated loss of endplate membrane rather than a direct effect of myasthenogenic antibodies on endplate Na(+) channels.