Quinidine inhibition of the muscarine receptor-activated K+ channel current in atrial cells of guinea pig

Summary Postsynaptic mechanisms underlying the anticholinergic effects of quinidine were examined in single atrial cells, using the tight-seal whole-cell recording technique. The solution in the glass pipettes contained guanosine-5triphosphate (GTP) or guanosine-5-O-(3-thiotriphosphate) (GTP-S, a non-hydrolyzable GTP analogue). In both cases, acetylcholine (ACh), applied to the bath, induced a specific K⁺ current. In GTP-loaded cells, quinidine in the bath solution depressed the ACh-induced K⁺ current concentration-dependently. Atropine also blocked the K⁺ current. On the other hand, in GTP-S-loaded cells, the ACh-induced current was not blocked by atropine and persisted even when ACh was washed out from the bath, indicating that GTP-S causes uncoupling of the K⁺ channels from the muscarine receptors. Quinidine, however, did depress the increased K⁺ current concentration-dependently. The percent inhibition curves for quinidine to depress the K⁺ current were very similar between GTP-loaded and GTP-S-loaded cells. From these observations, we suggest that direct inhibition of the muscarine receptor-activated K⁺ channel current by quinidine, and not blockade of the muscarine receptor itself, is mainly responsible for the anticholinergic effects of the drug in atrial myocytes.Send offprint requests to Y. Kurachi at the above address