The G protein-gated atrial K⁺ channel is stimulated by three distinct G_Iα-subunits

Abstract

The gunanine nucleotide-binding protein, G_i, which inhibits adenylyl cyclase, has recently been shown to have three subtypes of the a-subunit, termed G_iα-1, G_iα-2 and G_iα-3. They share 87–94% amino-acid sequence homology^1–10 and so are difficult to separate from one another. Among other functions^11,12–14, purified preparations activate K⁺ channels^15–21 but there is confusion over which of the subtypes activates the muscarinic K⁺ channels of the atrial muscle of the heart: G_iα-3, also termed G_k¹⁵, has been shown to activate this channel but it is not clear whether G_iα-l²² does²¹ or does not^23,24. To clarify this problem, we expressed the subtypes separately in Escherichia coli to eliminate contamination by other subtypes and tested the recombinant α- chains on atrial muscarinic K⁺ channels. Although we anticipated that only G_iα-3 would have G_kactivity, to our surprise all three recombinant subtypes were active, from which we deduce that the G_i subtypes are multifunctional.