Publication
Title
Dual effect of phosphatidyl (4,5)-bisphosphate $PIP_{2}$ on shaker $K^{+}$ channels
Author
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.
Language
English
Source (journal)
Journal of biological chemistry. - Baltimore, Md
Publication
Baltimore, Md : 2012
ISSN
0021-9258 [print]
1083-351X [online]
Volume/pages
287 :43 (2012) , p. 36158-36167
ISI
000310364000037
Full text (Publisher's DOI)
Full text (publisher's version - intranet only)
UAntwerpen
 Faculty/Department Research group Publication type Subject Affiliation Publications with a UAntwerp address