Quinidine inhibition of the muscarine receptor-activated K+ channel current in atrial cells of guinea pig.
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-5'-triphosphate (GTP) or guanosine-5'-O-(3-thiotriphosphate) (GTP-gamma 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-gamma 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-gamma 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-gamma 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.
D000109:Acetylcholine / Q000494:pharmacology; D000818:Animals; D001285:Atropine / Q000494:pharmacology; D016244:Guanosine 5'-O-(3-Thiotriphosphate); D006160:Guanosine Triphosphate / Q000031:analogs & derivatives / Q000494:pharmacology; D006168:Guinea Pigs; D006321:Heart / Q000187:drug effects; D066298:In Vitro Techniques; D007473:Ion Channels / Q000187:drug effects*; D009206:Myocardium / Q000378:metabolism*; D011802:Quinidine / Q000494:pharmacology*; D011976:Receptors, Muscarinic / Q000187:drug effects*; D013873:Thionucleotides / Q000494:pharmacology
D007473:Ion Channels; D011976:Receptors, Muscarinic; D013873:Thionucleotides; D016244:Guanosine 5'-O-(3-Thiotriphosphate); D001285:Atropine; D006160:Guanosine Triphosphate; D011802:Quinidine; D000109:Acetylcholine