Stereospecific modulation of the calcium channel in human erythrocytes by cholesterol and its oxidized derivatives

L. Neyses, R. Locher, M. Stimpel, R. Streuli, W. Vetter

    Research output: Contribution to journalArticlepeer-review

    Abstract

    To study the effect of cholesterol and its pathophysiologically important oxidized derivatives (OSC) on the calcium entry channel, the human red blood cell was used as a model system. The calcium ejecting adenosinetriphosphatase (ATPase) was inhibited by vanadate. The cells were loaded with OSC at concentrations between 1.25 X 10-5 and 25 X 10-5 mol/l. 22-Hydroxycholesterol, cholestan-3β,5α,6β-triol, 5α-cholestan-3β-ol,3β,5α-dihydroxycholestan-6-one and 3β-hydroxy-5α-cholestan-7-one stimulated 45Ca2+ influx by up to almost 90%, whereas 25-hydroxycholesterol, 7β-hydroxycholesterol, 20α-hydroxycholesterol and 7-oxocholesterol inhibited influx by up to 75%. Both stimulation and inhibition were dependent on the amount of OSC incorporated into the membrane. More than 90% of the total modification of calcium influx by OSC was accounted for by an influence on the nitrendipine-inhibitable part of influx. Enrichment of cholesterol in the membrane greatly stimulated, and cholesterol depletion inhibited, Ca2+ influx. These results demonstrate that cholesterol and its oxidized derivatives are able to modulate the calcium channel in human red blood cells in a highly stereospecific manner.
    Original languageEnglish
    Pages (from-to)105-112
    Number of pages7
    JournalBiochemical Journal
    Volume227
    Issue number1
    Publication statusPublished - 1985

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