Anti-cholinergic effect of verapamil on the muscarinic acetylcholine receptor-gated K+ channel in isolated guinea-pig atrial myocytes

Naunyn Schmiedebergs Arch Pharmacol. Jan-Feb 1989;339(1-2):244-6. doi: 10.1007/BF00165150.


Effects of verapamil on the acetylcholine (ACh)-induced K+ current were examined in single atrial cells, using the tight-seal whole-cell clamp technique. The pipette solution contained guanosine-5'-triphosphate (GTP) or guanosine-5'-O-(3-thiotriphosphate) (GTP-gamma S, a non-hydrolysable GTP analogue). In GTP-loaded cells, ACh induced a specific K+ current, which is known to be mediated by pertussis toxin-sensitive GTP-binding (G) proteins. Verapamil (0.1-100 microM) depressed the ACh-induced K+ current in a concentration-dependent fashion. In GTP-gamma S-loaded cells, the K+ current remained persistently after wash-out of ACh, probably due to irreversible activation of G proteins by GTP-gamma S. Verapamil (0.1-100 microM) also depressed the intracellular GTP-gamma S-induced K+ current. However, the magnitude of verapamil-depression of the K+ current in GTP-gamma S-loaded cells was significantly smaller than that in GTP-loaded cells at concentrations between 1 and 10 microM of the drug. From these results, it is suggested that verapamil may block not only the function of muscarinic ACh receptors but also of G proteins and/or the K+ channel itself and thereby depress the ACh-induced K+ current in isolated atrial myocytes.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Acetylcholine / antagonists & inhibitors
  • Animals
  • Guanosine 5'-O-(3-Thiotriphosphate)
  • Guanosine Triphosphate / analogs & derivatives
  • Guanosine Triphosphate / pharmacology
  • Guinea Pigs
  • Heart / drug effects*
  • In Vitro Techniques
  • Myocardium / cytology*
  • Myocardium / metabolism
  • Parasympatholytics*
  • Potassium Channels / drug effects*
  • Receptors, Cholinergic / drug effects*
  • Receptors, Muscarinic / drug effects*
  • Thionucleotides / pharmacology
  • Verapamil / pharmacology*


  • Parasympatholytics
  • Potassium Channels
  • Receptors, Cholinergic
  • Receptors, Muscarinic
  • Thionucleotides
  • Guanosine 5'-O-(3-Thiotriphosphate)
  • Guanosine Triphosphate
  • Verapamil
  • Acetylcholine