Short-term desensitization of muscarinic K+ channel current in isolated atrial myocytes and possible role of GTP-binding proteins

Pflugers Arch. 1987 Oct;410(3):227-33. doi: 10.1007/BF00580270.

Abstract

The short-term desensitization of the acetylcholine (ACh)-induced K+ channel current was examined in single atrial cells of guinea-pig heart. The tight-seal whole cell voltage clamp technique was used. The solution in the pipettes contained GTP or guanosine-5'-O-(3-thiotriphosphate) (GTP-gamma S, a non-hydrolyzable GTP analogue). In GTP-loaded cells, ACh evoked a specific K+ channel current via GTP-binding proteins (G) in a dose-dependent manner. The K+ current showed agonist-dependent desensitization similar to those reported in other cardiac tissues (Nilius 1983; Carmeliet and Mubagwa 1986). The cellular response to ACh was also desensitized by activation of P1-purinergic receptors with adenosine (Ado). In GTP-gamma S-loaded cells, the K+ current was gradually induced even in the absence of agonists, probably due to direct activation of G proteins by GTP-gamma S. In the early phase of the spontaneous current increase, ACh evoked a large current transiently. As the GTP-gamma S-induced activation of the current progressed, the magnitude of the ACh-evoked current transient became smaller and finally negligible. Similar results were obtained when Ado was used as an agonist instead of ACh to induce the K+ current. Therefore, it is indicated that the agonist-receptor interaction may not be essential for the desensitization of ACh-induced K+ current in atrial myocytes.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Acetylcholine / pharmacology*
  • Animals
  • Atrial Function
  • Drug Tolerance
  • Electric Conductivity
  • GTP-Binding Proteins / physiology*
  • Guanosine 5'-O-(3-Thiotriphosphate)
  • Guanosine Triphosphate / analogs & derivatives
  • Guanosine Triphosphate / pharmacology
  • Guinea Pigs
  • Heart / physiology*
  • Ion Channels / drug effects
  • Ion Channels / physiology*
  • Kinetics
  • Potassium / metabolism*
  • Receptors, Muscarinic / physiology*
  • Thionucleotides / pharmacology

Substances

  • Ion Channels
  • Receptors, Muscarinic
  • Thionucleotides
  • Guanosine 5'-O-(3-Thiotriphosphate)
  • Guanosine Triphosphate
  • GTP-Binding Proteins
  • Acetylcholine
  • Potassium