Click here to close
Hello! We notice that you are using Internet Explorer, which is not supported by Xenbase and may cause the site to display incorrectly.
We suggest using a current version of Chrome,
FireFox, or Safari.
Proc Natl Acad Sci U S A
2012 Sep 04;10936:E2399-408. doi: 10.1073/pnas.1207901109.
Show Gene links
Show Anatomy links
PIP2 controls voltage-sensor movement and pore opening of Kv channels through the S4-S5 linker.
Rodriguez-Menchaca AA
,
Adney SK
,
Tang QY
,
Meng XY
,
Rosenhouse-Dantsker A
,
Cui M
,
Logothetis DE
.
???displayArticle.abstract???
Voltage-gated K(+) (Kv) channels couple the movement of a voltage sensor to the channel gate(s) via a helical intracellular region, the S4-S5 linker. A number of studies link voltage sensitivity to interactions of S4 charges with membrane phospholipids in the outer leaflet of the bilayer. Although the phospholipid phosphatidylinositol-4,5-bisphosphate (PIP(2)) in the inner membrane leaflet has emerged as a universal activator of ion channels, no such role has been established for mammalian Kv channels. Here we show that PIP(2) depletion induced two kinetically distinct effects on Kv channels: an increase in voltage sensitivity and a concomitant decrease in current amplitude. These effects are reversible, exhibiting distinct molecular determinants and sensitivities to PIP(2). Gating current measurements revealed that PIP(2) constrains the movement of the sensor through interactions with the S4-S5 linker. Thus, PIP(2) controls both the movement of the voltage sensor and the stability of the open pore through interactions with the linker that connects them.
Bezanilla,
Gating of Shaker K+ channels: II. The components of gating currents and a model of channel activation.
1994, Pubmed,
Xenbase
Bezanilla,
Gating of Shaker K+ channels: II. The components of gating currents and a model of channel activation.
1994,
Pubmed
,
Xenbase
Börjesson,
Lipoelectric modification of ion channel voltage gating by polyunsaturated fatty acids.
2008,
Pubmed
,
Xenbase
Hamill,
Improved patch-clamp techniques for high-resolution current recording from cells and cell-free membrane patches.
1981,
Pubmed
Hansen,
Structural basis of PIP2 activation of the classical inward rectifier K+ channel Kir2.2.
2011,
Pubmed
Hess,
GROMACS 4: Algorithms for Highly Efficient, Load-Balanced, and Scalable Molecular Simulation.
2008,
Pubmed
Hilgemann,
The complex and intriguing lives of PIP2 with ion channels and transporters.
2001,
Pubmed
Huang,
Direct activation of inward rectifier potassium channels by PIP2 and its stabilization by Gbetagamma.
1998,
Pubmed
,
Xenbase
Jiang,
X-ray structure of a voltage-dependent K+ channel.
2003,
Pubmed
Kahraman,
Shape variation in protein binding pockets and their ligands.
2007,
Pubmed
Khalili-Araghi,
Calculation of the gating charge for the Kv1.2 voltage-activated potassium channel.
2010,
Pubmed
Kohout,
Electrochemical coupling in the voltage-dependent phosphatase Ci-VSP.
2010,
Pubmed
Ledwell,
Mutations in the S4 region isolate the final voltage-dependent cooperative step in potassium channel activation.
1999,
Pubmed
,
Xenbase
Liman,
Voltage-sensing residues in the S4 region of a mammalian K+ channel.
1991,
Pubmed
,
Xenbase
Logothetis,
Channelopathies linked to plasma membrane phosphoinositides.
2010,
Pubmed
Logothetis,
Incremental reductions of positive charge within the S4 region of a voltage-gated K+ channel result in corresponding decreases in gating charge.
1992,
Pubmed
,
Xenbase
Long,
Atomic structure of a voltage-dependent K+ channel in a lipid membrane-like environment.
2007,
Pubmed
Long,
Crystal structure of a mammalian voltage-dependent Shaker family K+ channel.
2005,
Pubmed
Lopes,
Alterations in conserved Kir channel-PIP2 interactions underlie channelopathies.
2002,
Pubmed
,
Xenbase
Loussouarn,
Phosphatidylinositol-4,5-bisphosphate, PIP2, controls KCNQ1/KCNE1 voltage-gated potassium channels: a functional homology between voltage-gated and inward rectifier K+ channels.
2003,
Pubmed
Milescu,
Interactions between lipids and voltage sensor paddles detected with tarantula toxins.
2009,
Pubmed
Morris,
Stereochemical quality of protein structure coordinates.
1992,
Pubmed
Murata,
Phosphoinositide phosphatase activity coupled to an intrinsic voltage sensor.
2005,
Pubmed
,
Xenbase
Oliver,
Functional conversion between A-type and delayed rectifier K+ channels by membrane lipids.
2004,
Pubmed
,
Xenbase
Oostenbrink,
Free energies of binding of polychlorinated biphenyls to the estrogen receptor from a single simulation.
2004,
Pubmed
Pathak,
Closing in on the resting state of the Shaker K(+) channel.
2007,
Pubmed
Ramu,
Enzymatic activation of voltage-gated potassium channels.
2006,
Pubmed
Rosenhouse-Dantsker,
Molecular characteristics of phosphoinositide binding.
2007,
Pubmed
Smith-Maxwell,
Role of the S4 in cooperativity of voltage-dependent potassium channel activation.
1998,
Pubmed
,
Xenbase
Stühmer,
Structural parts involved in activation and inactivation of the sodium channel.
1989,
Pubmed
,
Xenbase
Suh,
Regulation of ion channels by phosphatidylinositol 4,5-bisphosphate.
2005,
Pubmed
Villalba-Galea,
S4-based voltage sensors have three major conformations.
2008,
Pubmed
Wu,
Dual regulation of voltage-gated calcium channels by PtdIns(4,5)P2.
2002,
Pubmed
,
Xenbase
Xu,
Removal of phospho-head groups of membrane lipids immobilizes voltage sensors of K+ channels.
2008,
Pubmed
,
Xenbase
Zagotta,
Shaker potassium channel gating. II: Transitions in the activation pathway.
1994,
Pubmed
,
Xenbase
Zhang,
PIP(2) activates KCNQ channels, and its hydrolysis underlies receptor-mediated inhibition of M currents.
2003,
Pubmed
,
Xenbase
Zhang,
Activation of inwardly rectifying K+ channels by distinct PtdIns(4,5)P2 interactions.
1999,
Pubmed
,
Xenbase
