Activity and Stability of Panx1 Channels in Astrocytes and Neuroblastoma Cells Are Enhanced by Cholesterol Depletion

Antonio Cibelli, Eliana Scemes, David C. Spray

Research output: Contribution to journalArticlepeer-review

Abstract

Pannexin1 (Panx1) is expressed in both neurons and glia where it forms ATP-permeable channels that are activated under pathological conditions such as epilepsy, migraine, inflammation, and ischemia. Membrane lipid composition affects proper distribution and function of receptors and ion channels, and defects in cholesterol metabolism are associated with neurological diseases. In order to understand the impact of membrane cholesterol on the distribution and function of Panx1 in neural cells, we used fluorescence recovery after photobleaching (FRAP) to evaluate its mobility and electrophysiology and dye uptake to assess channel function. We observed that cholesterol extraction (using methyl-β-cyclodextrin) and inhibition of its synthesis (lovastatin) decreased the lateral diffusion of Panx1 in the plasma membrane. Panx1 channel activity (dye uptake, ATP release and ionic current) was enhanced in cholesterol-depleted Panx1 transfected cells and in wild-type astrocytes compared to non-depleted or Panx1 null cells. Manipulation of cholesterol levels may, therefore, offer a novel strategy by which Panx1 channel activation might modulate various pathological conditions.

Original languageEnglish (US)
Article number3219
JournalCells
Volume11
Issue number20
DOIs
StatePublished - Oct 2022

Keywords

  • ATP release
  • brain
  • cell biology
  • cholesterol
  • cyclodextrins
  • fluorescence recovery after photobleaching
  • membrane fluidity
  • membrane lipids
  • P2X7R
  • Panx1

ASJC Scopus subject areas

  • Biochemistry, Genetics and Molecular Biology(all)

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