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).
Du
Xiaona
X
Department of Pharmacology, Hebei Medical University, Shijiazhuang, China.
Zhang
Hailin
H
Lopes
Coeli
C
Mirshahi
Tooraj
T
Rohacs
Tibor
T
Logothetis
Diomedes E
DE
D000818:Animals; D018076:DNA, Complementary; D066246:ErbB Receptors / Q000378:metabolism*; D016297:Mutagenesis, Site-Directed; D019269:Phosphatidylinositol 4,5-Diphosphate / Q000378:metabolism*; D024661:Potassium Channels, Inwardly Rectifying / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D014982:Xenopus laevis
D018076:DNA, Complementary; C099489:KCNJ4 protein, human; D019269:Phosphatidylinositol 4,5-Diphosphate; D024661:Potassium Channels, Inwardly Rectifying; D066246:ErbB Receptors