Phospholipase C activation by anesthetics decreases membrane-cytoskeleton adhesion

D. Raucher, Michael Sheetz

Research output: Contribution to journalArticlepeer-review

46 Scopus citations

Abstract

Many different amphiphilic compounds cause an increase in the fluid-phase endocytosis rates of cells in parallel with a decrease in membrane-cytoskeleton adhesion. These compounds, however, do not share a common chemical structure, which leaves the mechanism and even site of action unknown. One possible mechanism of action is through an alteration of inositol lipid metabolism by modifying the cytoplasmic surface of the plasma membrane bilayer. By comparing permeable amphiphilic amines used as local anesthetics with their impermeable analogs, we find that access to the cytoplasmic surface is necessary to increase endocytosis rate and decrease membrane-cytoskeleton adhesion. In parallel, we find that the level of phosphatidylinositol 4,5-bisphosphate (PIP2) in the plasma membrane is decreased and cytoplasmic Ca2+ is increased only by permeable amines. The time course of both the decrease in plasma membrane PIP2 and the rise in Ca2+ parallels the decrease in cytoskeleton-membrane adhesion. Inositol labeling shows that phosphatidylinositol-4-phosphate levels are increased by the permeable anesthetics, indicating that lipid turnover is increased. Consistent with previous observations, phospholipase C (PLC) inhibitors block anesthetic effects on the PIP2 and cytoplasmic Ca2+ levels, as well as the drop in adhesion. Therefore, we suggest that PLC activity is increased by amine anesthetics at the cytoplasmic surface of the plasma membrane, which results in a decrease in membrane-cytoskeleton adhesion.

Original languageEnglish (US)
Pages (from-to)3759-3766
Number of pages8
JournalJournal of Cell Science
Volume114
Issue number20
StatePublished - Nov 20 2001
Externally publishedYes

Keywords

  • Calcium release
  • Local anesthetic
  • Membrane-cytoskeleton adhesion
  • Phospholipase C

ASJC Scopus subject areas

  • Cell Biology

Fingerprint Dive into the research topics of 'Phospholipase C activation by anesthetics decreases membrane-cytoskeleton adhesion'. Together they form a unique fingerprint.

Cite this