The G protein-gated atrial K+ channel is stimulated by three distinct Gi alpha-subunits.
The guanine nucleotide-binding protein, Gi, which inhibits adenylyl cyclase, has recently been shown to have three subtypes of the alpha-subunit, termed Gi alpha-1, Gi alpha-2 and Gi alpha-3. They share 87-94% amino-acid sequence homology and so are difficult to separate from one another. Among other functions, purified preparations activate K+ channels but there is confusion over which of the subtypes activates the muscarinic K+ channels of the atrial muscle of the heart: Gi alpha-3, also termed Gk, has been shown to activate this channel but it is not clear whether Gi alpha-1 does or does not. To clarify this problem, we expressed the subtypes separately in Escherichia coli to eliminate contamination by other subtypes and tested the recombinant alpha- chains on atrial muscarinic K+ channels. Although we anticipated that only Gi alpha-3 would have Gk activity, to our surprise all three recombinant subtypes were active, from which we deduce that the Gi subtypes are multifunctional.
D000818:Animals; D002417:Cattle; D004305:Dose-Response Relationship, Drug; D019204:GTP-Binding Proteins / Q000502:physiology*; D006168:Guinea Pigs; D006325:Heart Atria; D046911:Macromolecular Substances; D008722:Methods; D015221:Potassium Channels / Q000187:drug effects* / Q000378:metabolism; D011993:Recombinant Fusion Proteins / Q000494:pharmacology; D013268:Stimulation, Chemical; D013997:Time Factors
D046911:Macromolecular Substances; D015221:Potassium Channels; D011993:Recombinant Fusion Proteins; D019204:GTP-Binding Proteins