Receptor kinase-dependent desensitization of the muscarinic K+ current in rat atrial cells

J Physiol. 1995 Sep 1;487 ( Pt 2)(Pt 2):359-66. doi: 10.1113/jphysiol.1995.sp020885.


1. Activity of rat atrial muscarinic K+ channels has been measured in five configurations of the patch clamp technique. 2. In configurations in which the normal intracellular solution was lost, the slow phase of desensitization (a slow decline of channel activity during an exposure to ACh) was much reduced (or absent) and deactivation (on wash-off of ACh) was slowed as compared with desensitization and deactivation in configurations in which normal intracellular solution was retained. This suggests that soluble intracellular regulators are involved in these processes. 3. When a G protein-coupled receptor kinase (GRK2) was applied to the cytoplasmic surface of conventional outside-out patches in the presence of ATP, the slow phase of desensitization was restored. In the absence of ATP, GRK2 failed to restore the slow phase. 4. It is concluded that (i) G protein-coupled receptor kinase dependent phosphorylation of the muscarinic receptor is responsible for the slow phase of desensitization and (ii) a soluble factor (such as a GTPase activating protein or 'GAP') is responsible for normal rapid deactivation.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Acetylcholine / pharmacology
  • Animals
  • Cyclic AMP-Dependent Protein Kinases / metabolism*
  • Heart Atria / cytology
  • Heart Atria / drug effects
  • Heart Atria / metabolism*
  • In Vitro Techniques
  • Ion Channel Gating / drug effects
  • Ion Channel Gating / physiology*
  • Membrane Potentials / drug effects
  • Membrane Potentials / physiology
  • Patch-Clamp Techniques
  • Phosphorylation / drug effects
  • Potassium Channels / drug effects
  • Potassium Channels / metabolism*
  • Rats
  • Receptors, Muscarinic / drug effects
  • Receptors, Muscarinic / metabolism*
  • beta-Adrenergic Receptor Kinases


  • Potassium Channels
  • Receptors, Muscarinic
  • Cyclic AMP-Dependent Protein Kinases
  • beta-Adrenergic Receptor Kinases
  • Acetylcholine