Reference : Cholesterol and its oxidized derivatives modulate the calcium channel in human red bl...
Scientific journals : Article
Human health sciences : Cardiovascular & respiratory systems
Cholesterol and its oxidized derivatives modulate the calcium channel in human red blood cells.
Neyses, Ludwig mailto [University of Luxembourg > Research Office]
Stimpel, M. [> >]
Locher, R. [> >]
Streuli, R. [> >]
Kuffer, B. [> >]
Vetter, W. [> >]
Journal of Hypertension. Supplement)
Yes (verified by ORBilu)
[en] Calcium/blood ; Cholesterol/analogs & derivatives/blood/pharmacology ; Dose-Response Relationship, Drug ; Erythrocytes/drug effects/metabolism ; Humans ; Ion Channels/drug effects/metabolism ; Oxidation-Reduction
[en] The human red blood cell was used as a model system in order to study the effect of cholesterol and its medically important oxidized derivatives (OSC = oxidized sterol compounds) on the calcium entry channel. The calcium-ejecting adenosine triphosphatase (ATPase) was inhibited by vanadate and the influx of 45Ca2-into the cells measured. The cells were loaded with OSC at concentrations between 0.075 and 1.5 micrograms OSC/10(7) cells. Two classes of OSC could be distinguished: one stimulating Ca2+ influx dose-dependently by almost 100% at maximum concentrations, the other inhibiting it dose-dependently by up to 80%. The calcium channel blocker nitrendipine inhibited influx by 70% at 15 microM. More than 90% of the total stimulation or inhibition was accounted for by an influence on the nitrendipine-inhibitable part of influx, i.e. the calcium channel. Cholesterol (incorporated using liposomes) had a stimulatory (+288%), cholesterol depletion an inhibitory effect on calcium influx (-18%). These results demonstrate that cholesterol and its oxidized derivatives modulate the calcium channel in a highly stereospecific manner and provide new insights into the mechanism of action and the atherogenic effect of these compounds.

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