Compromised ATP binding as a mechanism of phosphoinositide modulation of ATP-sensitive K+ channels

Congmiao Wang, Kun Wang, Wenxia Wang, Yijun Cui, Zheng Fan

Research output: Contribution to journalArticle

20 Citations (Scopus)

Abstract

Inhibition of ATP-sensitive K+ (KATP) channels by ATP, a process presumably initiated by binding of ATP to the pore-forming subunit, Kir6.2, is reduced in the presence of phosphoinositides (PPIs). Previous studies led to the hypothesis that PPIs compromise ATP binding. Here, this hypothesis was tested using purified Kir6.2. We show that PPIs bind purified Kir6.2 in an isomer-specific manner, that biotinylated ATP analogs photoaffinity label purified Kir6.2, and that this labeling is weakened in the presence of PPIs. Patch-clamp measurements confirmed that these ATP analogs inhibited Kir6.2 channels, and that PPIs decreased the level of inhibition. These results indicate that interaction of PPIs with Kir6.2 impedes ATP-binding activity. The PPI regulation of ATP binding revealed in this study provides a putative molecular mechanism that is potentially pivotal to the nucleotide sensitivity of KATP channels.

Original languageEnglish (US)
Pages (from-to)177-182
Number of pages6
JournalFEBS Letters
Volume532
Issue number1-2
DOIs
StatePublished - Dec 4 2002

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Phosphatidylinositols
Adenosine Triphosphate
Modulation
KATP Channels
Photoaffinity Labels
Clamping devices
Isomers
Labeling
Nucleotides

All Science Journal Classification (ASJC) codes

  • Structural Biology
  • Biophysics
  • Biochemistry
  • Molecular Biology
  • Genetics
  • Cell Biology

Cite this

Compromised ATP binding as a mechanism of phosphoinositide modulation of ATP-sensitive K+ channels. / Wang, Congmiao; Wang, Kun; Wang, Wenxia; Cui, Yijun; Fan, Zheng.

In: FEBS Letters, Vol. 532, No. 1-2, 04.12.2002, p. 177-182.

Research output: Contribution to journalArticle

Wang, Congmiao ; Wang, Kun ; Wang, Wenxia ; Cui, Yijun ; Fan, Zheng. / Compromised ATP binding as a mechanism of phosphoinositide modulation of ATP-sensitive K+ channels. In: FEBS Letters. 2002 ; Vol. 532, No. 1-2. pp. 177-182.
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