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

Xiaona Du, Hailin Zhang, Coeli Lopes, Tooraj Mirshahi, Tibor Rohacs, Diomedes E Logothetis

J. Biol. Chem., 2004 Sep 3 , 279, 37271-81

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).

http://www.ncbi.nlm.nih.gov/pubmed/15155739