Quinidine normalizes the open duration of slow-channel mutants of the acetylcholine receptor

QUINIDINE is a long-lived open-channel blocker of the wild-type endplate acetylcholine receptor (AChR). To test the hypothesis that quinidine can normalize the prolonged channel opening events of slow-channel mutants of human AChR, we expressed wild-type AChR and five well characterized slow-channel mutants of AChR in HEK 293 cells and monitored the effects of quinidine on acetylcholine-induced channel currents. Quinidine shortens the longest component of channel opening burst (tau(3b)) Of both wild-type and mutant AChRs in a concentration-dependent manner, and 5 mu M quinidine reduces tau(3b) Of the mutant AChRs to that elf wild-type AChRs in the absence of quinidine. Because this concentration of quinidine is attainable in clinical practice, the findings predict a therapeutic effect for quinidine in the slow-channel congenital myasthenic syndrome. (C) 1998 Rapid Science Ltd.