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 (τ(3b)) of both wild-type and mutant AChRs in a concentration-dependent manner, and 5 μM quinidine reduces τ(3b) of the mutant AChRs to that of 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.
- Acetylcholine receptor
- Channel block
- Slow channel congenital myasthenic syndrome
ASJC Scopus subject areas