Characteristic Interactions with Phosphatidylinositol 4,5-Bisphosphate Determine Regulation of Kir Channels by Diverse Modulators

Abstract

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 ␤␥-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 .

Mutations in Nature Conferred a High Affinity Phosphatidylinositol 4,5-Bisphosphate-binding Site in Vertebrate Inwardly Rectifying Potassium Channels

“…2C). Notably, Kir2.1 has a higher affinity for PIP 2 interaction than does Kir2.3 (41). Third, when muscarinic (M1) acetylcholine receptors were co-expressed with AqKir and activated by acetylcholine, the inward AqKir K ϩ currents were inhibited (Fig.…”

Membrane Depolarization Increases Membrane PtdIns(4,5)P2 Levels through Mechanisms Involving PKC βII and PI4 Kinase

“…Xenopus Oocyte Isolation and cRNA Injection-Oocytes were surgically isolated from anesthetized adult female frogs (Xenopus laevis) as previously described (17) and treated with 2 mg/ml collagenase (Type II, Sigma) in OR 2 solution (in mM: 82.5 NaCl, 2 KCl, 1 MgCl 2 , 5 HEPES, pH 7.4) for 90 min at room temperature (ϳ25°C). After three washes with OR 2 solution, the oocytes were incubated at 18°C in ND96 solution (in mM: 96 NaCl, 1 KCl, 1 MgCl 2 , 1.8 CaCl 2 , and 5 HEPES, pH 7.4).…”

Expression of inwardly rectifying potassium channel subunits in native human retinal pigment epithelium

“…Although all Kir channel subtypes expressed in the RPE are gated by PIP 2 , they differ in their sensitivity: Kir2.1 has a high affinity for PIP 2 , whereas members of the Kir3, Kir6 and Kir7 subfamilies have relatively low affinities and, hence, can be inhibited by phospholipase Cmediated decreases in the membrane content of PIP 2 (Huang et al, 1998;Zhang et al, 1999;Rohacs et al, 1999;Hilgemann and Ball, 1996;Shyng and Nichols, 1998;Baukrowitz et al, 1998;Du et al, 2004). The Kir current in bovine RPE is inhibited by ATP depletion (Hughes and Takahira, 1998), and recent evidence suggests that this is a consequence of a decrease in the regeneration of membrane PIP 2 by phosphoinositol 4-kinase, a process that is dependent on ATP hydrolysis (Pattnaik and Hughes, 2006).…”