Title
Dual effect of phosphatidyl (4,5)-bisphosphate <tex>$PIP_{2}$</tex> on shaker <tex>$K^{+}$</tex> channels Dual effect of phosphatidyl (4,5)-bisphosphate <tex>$PIP_{2}$</tex> on shaker <tex>$K^{+}$</tex> channels
Author
Faculty/Department
Faculty of Pharmaceutical, Biomedical and Veterinary Sciences . Biomedical Sciences
Publication type
article
Publication
Baltimore, Md ,
Subject
Chemistry
Biology
Source (journal)
Journal of biological chemistry. - Baltimore, Md
Volume/pages
287(2012) :43 , p. 36158-36167
ISSN
0021-9258
ISI
000310364000037
Carrier
E
Target language
English (eng)
Full text (Publishers DOI)
Affiliation
University of Antwerp
Abstract
Phosphatidylinositol (4,5)-bisphosphate (PIP2) is a phospholipid of the plasma membrane that has been shown to be a key regulator of several ion channels. Functional studies and more recently structural studies of Kir channels have revealed the major impact of PIP2 on the open state stabilization. A similar effect of PIP2 on the delayed rectifiers Kv7.1 and Kv11.1, two voltage-gated K+ channels, has been suggested, but the molecular mechanism remains elusive and nothing is known on PIP2 effect on other Kv such as those of the Shaker family. By combining giant-patch ionic and gating current recordings in COS-7 cells, and voltage-clamp fluorimetry in Xenopus oocytes, both heterologously expressing the voltage-dependent Shaker channel, we show that PIP2 exerts 1) a gain-of-function effect on the maximal current amplitude, consistent with a stabilization of the open state and 2) a loss-of-function effect by positive-shifting the activation voltage dependence, most likely through a direct effect on the voltage sensor movement, as illustrated by molecular dynamics simulations.
E-info
https://repository.uantwerpen.be/docman/iruaauth/77957a/94d3069.pdf
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