PIP2 controls voltage-sensor movement and pore opening of Kv channels through the S4–S5 linker

Aldo A. Rodriguez-Menchaca, Scott K. Adney, Qiong Yao Tang, Xuan Yu Meng, Avia Rosenhouse-Dantsker, Meng Cui, Diomedes E. Logothetis*

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

76 Scopus citations

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 (PIP2) 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 PIP2 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 PIP2. Gating current measurements revealed that PIP2 constrains the movement of the sensor through interactions with the S4–S5 linker. Thus, PIP2 controls both the movement of the voltage sensor and the stability of the open pore through interactions with the linker that connects them.

Original languageEnglish (US)
Pages (from-to)E2399-E2408
JournalProceedings of the National Academy of Sciences of the United States of America
Volume109
Issue number36
DOIs
StatePublished - Aug 13 2012

Keywords

  • Channel modulation
  • Lipids
  • Open probability
  • Voltage-gated channels

ASJC Scopus subject areas

  • General

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