Modulation of Kv3.1b potassium channel level and intracellular potassium concentration in 158N murine oligodendrocytes and BV-2 murine microglial cells treated with 7-ketocholesterol, 24S-hydroxycholesterol or tetracosanoic acid (C24:0)

Biochimie. 2018 Oct;153:56-69. doi: 10.1016/j.biochi.2018.02.008. Epub 2018 Feb 17.

Abstract

Little is known about K+ regulation playing major roles in the propagation of nerve impulses, as well as in apoptosis and inflammasome activation involved in neurodegeneration. As increased levels of 7-ketocholesterol (7KC), 24S-hydroxycholesterol (24S-OHC) and tetracosanoic acid (C24:0) have been observed in patients with neurodegenerative diseases, we studied the effect of 24 and/or 48 h of treatment with 7KC, 24S-OHC and C24:0 on Kv3.1b potassium channel level, intracellular K+ concentration, oxidative stress, mitochondrial dysfunction, and plasma membrane permeability in 158N oligodendrocytes and BV-2 microglial cells. In 158N cells, whereas increased level of Kv3.1b was only observed with 7KC and 24S-OHC but not with C24:0 at 24 h, an intracellular accumulation of K+ was always detected. In BV-2 cells treated with 7KC, 24S-OHC and C24:0, Kv3.1b level was only increased at 48 h; intracellular K+ accumulation was found at 24 h with 7KC, 24S-OHC and C24:0, and only with C24:0 at 48 h. Positive correlations between Kv3.1b level and intracellular K+ concentration were observed in 158N cells in the presence of 7KC and 24S-OHC, and in 7KC-treated BV-2 cells at 48 h. Positive correlations were also found between Kv3.1b or the intracellular K+ concentration, overproduction of reactive oxygen species, loss of transmembrane mitochondrial potential and increased plasma membrane permeability in 158N and BV-2 cells. Our data support that the lipid environment affects Kv3.1b channel expression and/or functionality, and that the subsequent rupture of K+ homeostasis is relied with oligodendrocytes and microglial cells damages.

Keywords: 158N cells; 24S-hydroxycholesterol; 7-Ketocholesterol; BV-2 cells; Kv3.1b; Oxysterols; Potassium; Tetracosanoic acid (C24:0).

MeSH terms

  • Animals
  • Cell Line, Transformed
  • Fatty Acids / pharmacology*
  • Hydroxycholesterols / pharmacology*
  • Ketocholesterols / pharmacology*
  • Male
  • Mice
  • Microglia / metabolism*
  • Mitochondria / drug effects
  • Oligodendroglia / drug effects*
  • Oligodendroglia / metabolism
  • Potassium / metabolism*
  • Reactive Oxygen Species / metabolism
  • Shaw Potassium Channels / metabolism*

Substances

  • Fatty Acids
  • Hydroxycholesterols
  • Kcnc1 protein, mouse
  • Ketocholesterols
  • Reactive Oxygen Species
  • Shaw Potassium Channels
  • 24-hydroxycholesterol
  • 7-ketocholesterol
  • lignoceric acid
  • Potassium