Specificity of Gbetagamma signaling depends on Galpha subunit coupling with G-protein-sensitive K(+) channels.
Many neurotransmitters activate G-protein-gated inwardly rectifying K(+) (Kir3) channels by stimulating G-protein-coupled receptors. However, in native systems, only receptors coupled to pertussis-toxin (PTX)-sensitive G proteins (Gi/Go) have been shown to be able to activate Kir3 channels through the betagamma subunits of G proteins (Gbetagamma), whereas activation of receptors coupled to PTX-insensitive G proteins such as Gq or Gs do not activate Kir3 channels. The question remains as to how signaling specificity is achieved and what are its key determinants. In this study, we have used the Xenopus oocyte expression system to investigate specific activation of Kir3 channels by heterotrimeric G proteins. We have demonstrated the activation of Kir3.4 channels by agonist stimulation of non-PTX-sensitive G proteins under conditions of Galpha subunit overexpression. We present evidence to suggest a key role for the coupling efficiency of Galpha subunits in determining the specificity of Gbetagamma signaling to the channel.
Geng
Xian
X
Department of Pharmacology, Hebei Medical University, Shijiazhuang, People's Republic of China.
Du
Xiao-na
XN
Rusinova
Radda
R
Liu
Bo-yi
BY
Li
Fang
F
Zhang
Xuan
X
Chen
Xing-juan
XJ
Logothetis
Diomedes E
DE
Zhang
Hai-lin
HL
D000818:Animals; D005260:Female; D051676:G Protein-Coupled Inwardly-Rectifying Potassium Channels / Q000819:agonists / Q000235:genetics / Q000378:metabolism*; D044385:GTP-Binding Protein alpha Subunits / Q000235:genetics / Q000378:metabolism*; D015870:Gene Expression; D020962:Heterotrimeric GTP-Binding Proteins / Q000378:metabolism*; D009865:Oocytes; D037342:Pertussis Toxin / Q000494:pharmacology; D015398:Signal Transduction; D014982:Xenopus laevis
D051676:G Protein-Coupled Inwardly-Rectifying Potassium Channels; D044385:GTP-Binding Protein alpha Subunits; D037342:Pertussis Toxin; D020962:Heterotrimeric GTP-Binding Proteins