Anionic phospholipids activate ATP-sensitive potassium channels

Zheng Fan, Jonathan C. Makielski

Research output: Contribution to journalArticle

264 Citations (Scopus)

Abstract

The ATP-sensitive potassium channel (KATP) controls insulin release in pancreatic β-cells and also modulates important functions in other cell types. In this study we report that anionic phospholipids activated KATP in pancreatic β-cells, cardiac myocytes, skeletal muscle cells, and a cloned KATP composed of two subunits (SUR/Kir6.2) stably expressed in a mammalian cell line. The effectiveness was proportional to the number of negative charges on the head group of the anionic phospholipid. Screening negative charges with polyvalent cations antagonized the effect. Enzymatic treatment with phospholipases that reduced charge on the lipids also reduced or eliminated the effect. These results suggest that intact phospholipids with negative charges are the critical requirement for activation of KATP, in distinction from the usual cell signaling pathway through phospholipids that requires cleavage. Mutations of two positively charged amino acid residues at the C terminus of Kir6.2 accelerated loss of channel activity and reduced the activating effects of phospholipids, suggesting involvement of this region in the activation. Metabolism of anionic phospholipids in plasmalemmal membrane may be a novel and general mechanism for regulation of KATP and perhaps other ion channels in the family of inward rectifiers.

Original languageEnglish (US)
Pages (from-to)5388-5395
Number of pages8
JournalJournal of Biological Chemistry
Volume272
Issue number9
DOIs
StatePublished - Feb 28 1997
Externally publishedYes

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KATP Channels
Phospholipids
Chemical activation
Cells
Cell signaling
Phospholipases
Ion Channels
Cardiac Myocytes
Metabolism
Muscle Cells
Muscle
Cations
Screening
Skeletal Muscle
Insulin
Membranes
Lipids
Amino Acids
Cell Line
Mutation

All Science Journal Classification (ASJC) codes

  • Biochemistry

Cite this

Anionic phospholipids activate ATP-sensitive potassium channels. / Fan, Zheng; Makielski, Jonathan C.

In: Journal of Biological Chemistry, Vol. 272, No. 9, 28.02.1997, p. 5388-5395.

Research output: Contribution to journalArticle

Fan, Zheng ; Makielski, Jonathan C. / Anionic phospholipids activate ATP-sensitive potassium channels. In: Journal of Biological Chemistry. 1997 ; Vol. 272, No. 9. pp. 5388-5395.
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