Authors: Wu Deng Rahul Mahajan Clive M Baumgarten Diomedes E Logothetis
Publish Date: 2016/02/02
Volume: 468, Issue: 5, Pages: 817-824
Abstract
Inwardly rectifying K+ Kir channels are important contributors to the resting membrane potential and regulate cellular excitability The activity of Kir channels depends critically on the phospholipid PIP2 Several modulators of the activity of Kir channels alter the apparent affinity of the channel to PIP2 Channels with high apparent affinity to PIP2 may not respond to a given modulator but mutations that decrease such affinity can render the channel susceptible to modulation Here we identify a known inhibitor of the swellingactivated Cl− current DCPIB as an effective inhibitor of a number of Kir channels both in native cardiac cells and in heterologous expression systems We show that the apparent affinity to PIP2 determines whether DCPIB will serve as an efficient blocker of Kir channels These effects are consistent with a model in which DCPIB competes with PIP2 for a common binding siteThe authors are grateful to Heikki Vaananen and Sophia Gruszecki for oocyte isolation Thanks to all the members of the Logothetis laboratory for critical feedback on this work at every stage of its development The work was supported by National Institutes of Health grants R01HL5994918 and R01HL0908824 to DEL WD was supported by NIH training grant T32HL094290 Lipid Signaling and Functional Lipidomics in Cardiovascular and Respiratory Diseases LCRD RM was supported by predoctoral NRSA fellowship F30HL097582 from NHLBI
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