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KMID : 0811720070110000091
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Korean Journal of Physiology & Pharmacology
2007 Volume.11 No. 0 p.91 ~ p.0
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Oxidized LDL and Its Major Lipid Constituent Lysophosphatidylcholine Increase Intracellular Ca2+ through Store-Operated Ca2+ Entry
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Kim Moon-Young
Liang Guo Hua
Park Seong-Hee
Suh Suk-Hyo
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Abstract
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The effects of oxidized low-density lipoprotein (oxLDL) and its major lipid constituent lysophosphatidylcholine (LPC) on store operated Ca2+ entry (SOC) were investigated in cultured human umbilical endothelial cells (HUVECs) using fura-2 fluorescence and patch-clamp methods. OxLDL or LPC increased intracellular Ca2+ concentration ([Ca2+]i). An increase in [Ca2+]i by oxLDL or by LPC was inhibited by La3+ or by depletion of extracellular Ca2+. In addition, SOC, which was evoked by intracellular Ca2+ store depletion in Ca2+-free solution using the sarcoplasmic reticulum Ca2+ pump blocker, 2, 5-di-t-butyl-1, 4-benzohydroquinone (BHQ), was further enhanced by oxLDL or by LPC. Increased SOC by oxLDL or by LPC was inhibited by La3+ but not inhibited by 2-APB. In voltage-clamped cells, oxLDL or LPC activated non-selective cation (NSC) current. In addition, NSC current, which was activated by clamping internal Ca2+ to 1μM, was further enhanced by oxLDL or by LPC. Furthermore, NSC current was activated by various agonists including ATP to increase endothelial [Ca2+]i and was completely abolished by depleting external Ca2+. In voltage-clamped HUVECs, oxLDL enhanced SOC and evoked outward currents simultaneously. Clamping internal Ca2+ to 1μM spontaneously activated large-conductance Ca2+-activated K+ (BKCa) current and this activated BKCa current was further enhanced by oxLDL or by LPC. From these results, we concluded that oxLDL or its main component LPC activates Ca2+- permeable Ca2+-activated NSC current and BKCa current simultaneously and thereby increases SOC.
Source: Korean Journal of Physiology & Pharmacology.2007 Oct;11(Suppl II):S84-S84
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KEYWORD
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oxidized LDL, endothelial cell, store-operated Ca2+ entry, large conductance Ca2+-activated K+ channel, nonselective cation current
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