G protein-coupled receptor kinase mediates desensitization of norepinephrine-induced Ca2+ channel inhibition

Neuron. 1996 Mar;16(3):579-85. doi: 10.1016/s0896-6273(00)80077-x.


G protein-coupled receptors are essential signaling molecules at sites of synaptic transmission. Here, we explore the mechanisms responsible for the use-dependent termination of metabotropic receptor signaling in embryonic sensory neurons. We report that the inhibition of voltage-dependent Ca2+ channels mediated by alpha2-adrenergic receptors desensitizes slowly with prolonged exposure to the transmitter and that the desensitization is mediated by a G protein-coupled receptor kinase (GRK). Intracellular introduction of recombinant, purified kinases or synthetic blocking peptides into individual neurons demonstrates the specific involvement of a GRK3-like protein. These results suggest that GRK-mediated termination of receptor-G protein coupling is likely to regulate synaptic strength and, as such, may provide one effective mechanism for depression of synaptic transmission.

Publication types

  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Animals
  • Calcium Channels / drug effects*
  • Cells, Cultured
  • Chick Embryo
  • Dose-Response Relationship, Drug
  • GTP-Binding Proteins / physiology*
  • Norepinephrine / pharmacology*
  • Patch-Clamp Techniques
  • Phosphorylation
  • Protein Kinases / pharmacology*
  • Synaptic Transmission / physiology


  • Calcium Channels
  • Protein Kinases
  • GTP-Binding Proteins
  • Norepinephrine