Self repair in a zebrafish model for slow-channel myasthenic syndrome

Slow channel syndrome (SCS) is a congenital myasthenic disorder caused by mutations in nicotinic acetylcholine receptor (AChR) subunits, prolonging channel openings and impairing neuromuscular transmission. Using the zebrafish twister mutant, which mimics human SCS but undergoes natural recovery, we identified two abnormal kinetic components linked to embryonic and adult AChR isoforms. Recovery occurs via developmental replacement of embryonic subunits, restoring synaptic function. Blocking embryonic subunit translation accelerated recovery, and quinidine, an open-channel blocker, improved motility by normalizing synaptic current decay. These findings reveal mechanisms of SCS pathogenesis and suggest therapeutic strategies for myasthenic syndromes.