Characteristic interactions with phosphatidylinositol 4,5-bisphosphate determine regulation of kir channels by diverse modulators.

The activity of specific inwardly rectifying potassium (Kir) channels is regulated by any of a number of different modulators, such as protein kinase C, G(q) -coupled receptor stimulation, pH, intracellular Mg(2+) or the betagamma-subunits of G proteins. Phosphatidylinositol 4,5-bisphosphate (PIP(2)) is an essential factor for maintenance of the activity of all Kir channels. Here, we demonstrate that the strength of channel-PIP(2) interactions determines the sensitivity of Kir channels to regulation by the various modulators. Furthermore, our results suggest that differences among Kir channels in their specific regulation by a given modulator may reflect differences in their apparent affinity of interactions with PIP(2).