Changes in membrane cholesterol of pituitary tumor (GH 3 ) cells regulate the activity of large-conductance Ca 2+ -activated K + channels

Ming Wei Lin, Adonis Z. Wu, Wen Hung Ting, Ching Lin Li, Kuo Sheng Cheng, Sheng Nan Wu

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The effects of changes in membrane cholesterol on ion currents were investigated in pituitary GH 3 cells. Depletion of membrane cholesterol by exposing cells to methyl-β-cyclodextrin (MβCD), an oligosaccharide, resulted in an increase in the density of Ca 2+ -activated K + current (I K(Ca) ). However, no significant change in I K(Ca) density was demonstrated in GH 3 cells treated with a mixture of MβCD and cholesterol. Cholesterol depletion with MβCD (1.5 mg/ml) slightly suppressed the density of voltage-dependent L-type Ca 2+ current. In inside-out patches recorded from MβCD-treated cells, the activity of large-conductance Ca 2+ -activated K + (BK Ca ) channels was enhanced with no change in single-channel conductance. In MβCD-treated cells, voltage-sensitivity of BK Ca channels was increased; however, no change in Ca 2+ -sensitivity could be demonstrated. A negative correlation between adjacent closed and open times in BK Ca channels was observed in MβCD-treated cells. In inside-out patches from MβCD-treated cells, dexamethasone (30 μM) applied to the intracellular surface did not increase BK Ca -channel activity, although caffeic acid phenethyl ester and cilostazol still opened its probability effectively. However, no modification in the activity of ATP-sensitive K + channels could be seen in MβCD-treated cells. Current-clamp recordings demonstrated that the cholesterol depletion maneuver with MβCD reduced the firing of action potentials. Therefore, the increase in BK Ca -channel activity induced by membrane depletion may influence the functional activities of neurons or neuroendocrine cells if similar results occur in vivo.

Original languageEnglish
Pages (from-to)1-13
Number of pages13
JournalChinese Journal of Physiology
Issue number1
Publication statusPublished - 2006 Jan 1

All Science Journal Classification (ASJC) codes

  • Physiology
  • Physiology (medical)

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