题名

Changes in Membrane Cholesterol of Pituitary Tumor (GH3) Cells Regulate the Activity of Large-Conductance Ca(superscript 2+)-Activated K(superscript +) Channels

作者

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

关键词

methyl-β-cyclodextrin ； cholesterol ； Ca(superscript 2+)-activated K(superscript +) current ； large-conductance Ca(superscript 2+)-activated K(superscript +) channels ； GH3 cells

期刊名称

The Chinese Journal of Physiology

卷期/出版年月

49卷1期（2006 / 02 / 28）

页次

1 - 13

内容语文

英文
英文摘要

The effects of changes in membrane cholesterol on ion currents were investigated in pituitary GH3 cells. Depletion of membrane cholesterol by exposing cells to methyl-β-cyclodextrin (MβCD), an oligosaccharide, resulted in an increase in the density of Ca(superscript 2+)-activated K(superscript +) current (I(subscript K(Ca))). However, no significant change in I(subscript K(Ca)) density was demonstrated in GH3 cells treated with a mixture of MβCD and cholesterol. Cholesterol depletion with MβCD (1.5mg/ml) slightly suppressed the density of voltage-dependent L-type Ca(superscript 2+) current. In inside-out patches recorded from MβCD-treated cells, the activity of large-conductance Ca(superscript 2+)-activated K(superscript +) (BK(subscript Ca)) channels was enhanced with no change in single-channel conductance. In MβCD-treated cells, voltage-sensitivity of BK(subscript Ca) channels was increased; however, no change in Ca(superscript 2+)-sensitivity could be demonstrated. A negative correlation between adjacent closed and open times in BK(subscript Ca) channels was observed in MβCD-treated cells. In inside-out patches from MβCD-treated cells, dexamethasone (30μM) applied to the intracellular surface did not increase BK(subscript 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(superscript +) 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(subscript Ca)-channel activity induced by membrane depletion may influence the functional activities of neurons or neuroendocrine cells if similar results occur in vivo.
主题分类 醫藥衛生 > 基礎醫學
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