QUINIDINE NORMALIZES THE OPEN DURATION OF SLOW-CHANNEL MUTANTS OF THEACETYLCHOLINE-RECEPTOR

QUINIDINE is a long-lived open-channel blocker of the wild-type endpla te acetylcholine receptor (AChR). To test the hypothesis that quinidin e can normalize the prolonged channel opening events of slow-channel m utants of human AChR, we expressed wild-type AChR and five well charac terized slow-channel mutants of AChR in HEK 293 cells and monitored th e effects of quinidine on acetylcholine-induced channel currents. Quin idine shortens the longest component of channel opening burst (tau(3b) ) Of both wild-type and mutant AChRs in a concentration-dependent mann er, and 5 mu M quinidine reduces tau(3b) Of the mutant AChRs to that e lf wild-type AChRs in the absence of quinidine. Because this concentra tion of quinidine is attainable in clinical practice, the findings pre dict a therapeutic effect for quinidine in the slow-channel congenital myasthenic syndrome. (C) 1998 Rapid Science Ltd.