The G protein alpha subunit has a key role in determining the specificity of coupling to, but not the activation of, G protein-gated inwardly rectifying K+ channels

In neuronal and atrial tissue, G protein-gated inwardly rectifying K+ chann els (Kir3.x family) are responsible for mediating inhibitory postsynaptic p otentials and slowing the heart rate, They are activated by G beta gamma di mers released in response to the stimulation of receptors coupled to inhibi tory G proteins of the G(i/o) family but not receptors coupled to the stimu latory G protein G(s), We have used biochemical, electrophysiological, and molecular biology techniques to examine this specificity of channel activat ion. In this study we have succeeded in reconstituting such specificity in an heterologous expression system stably expressing a cloned counterpart of the neuronal channel (Kir3.1 and Kir3.2A heteromultimers), The use of pert ussis toxin-resistant G protein alpha subunits and chimeras between G(il) a nd G(s) indicate a central role for the G protein alpha subunits in determi ning receptor specificity of coupling to, but not activation of, G protein- gated inwardly rectifying K+ channels.