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

Naunyn Schmiedebergs Arch Pharmacol. 1987 Feb;335(2):216-8. doi: 10.1007/BF00177726.


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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Acetylcholine / pharmacology
  • Animals
  • Atropine / pharmacology
  • Guanosine 5'-O-(3-Thiotriphosphate)
  • Guanosine Triphosphate / analogs & derivatives
  • Guanosine Triphosphate / pharmacology
  • Guinea Pigs
  • Heart / drug effects
  • In Vitro Techniques
  • Ion Channels / drug effects*
  • Myocardium / metabolism*
  • Quinidine / pharmacology*
  • Receptors, Muscarinic / drug effects*
  • Thionucleotides / pharmacology


  • Ion Channels
  • Receptors, Muscarinic
  • Thionucleotides
  • Guanosine 5'-O-(3-Thiotriphosphate)
  • Atropine
  • Guanosine Triphosphate
  • Quinidine
  • Acetylcholine