Dominant negative effects of a Gbeta mutant on G-protein coupled inward rectifier K+ channel

FEBS Lett. 2006 Jul 10;580(16):3879-82. doi: 10.1016/j.febslet.2006.06.016. Epub 2006 Jun 16.

Abstract

HEK293 cells were transfected with cDNAs for Gbeta1(W332A) [a mutant Gbeta1], Ggamma2, and inward rectifier K+ channels (Kir3.1/Kir3.2). Application of Gbeta1gamma2 protein to these cells activated the K+ channels only slightly. When mu-opioid receptors and Kir3.1/Kir3.2 were transfected, application of a mu-opioid agonist induced a Kir3 current. However, co-expression of Gbeta1(W332A) suppressed this current. Most likely, Gbeta1(W332A) inhibited the action of the endogenous Gbeta. Such a dominant negative effect of Gbeta1(W332A) was also observed in neuronal Kir3 channels in locus coeruleus. The mutant, Gbeta1(W332A) protein, although inactive, retains its ability to bind Kir3 and prevents the wild type Gbeta from activating the channel.

Publication types

  • Research Support, N.I.H., Extramural

MeSH terms

  • Animals
  • Cattle
  • G Protein-Coupled Inwardly-Rectifying Potassium Channels / metabolism*
  • GTP-Binding Protein beta Subunits / genetics*
  • GTP-Binding Protein beta Subunits / metabolism*
  • GTP-Binding Protein gamma Subunits / metabolism
  • Genes, Dominant / genetics*
  • Humans
  • Locus Coeruleus / physiology
  • Mice
  • Mutation / genetics*
  • Rats
  • Rats, Long-Evans
  • Receptors, Opioid, mu / metabolism
  • Time Factors

Substances

  • G Protein-Coupled Inwardly-Rectifying Potassium Channels
  • GTP-Binding Protein beta Subunits
  • GTP-Binding Protein gamma Subunits
  • Receptors, Opioid, mu