title: Stereospecific modulation of the calcium channel in human erythrocytes by cholesterol and its oxidized derivatives.
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-3 beta,5 alpha,6 beta-triol, 5 alpha-cholestan-3 beta-ol,3 beta,5 alpha-dihydroxycholestan-6-one and 3 beta-hydroxy-5 alpha-cholestan-7-one stimulated 45Ca2+ influx by up to almost 90%, whereas 25-hydroxycholesterol, 7 beta-hydroxycholesterol, 20 alpha-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.
authors.forename: L
authors.initials: L
authors.lastname: Neyses
authors.forename: R
authors.initials: R
authors.lastname: Locher
authors.forename: M
authors.initials: M
authors.lastname: Stimpel
authors.forename: R
authors.initials: R
authors.lastname: Streuli
authors.forename: W
authors.initials: W
authors.lastname: Vetter
mesh_terms: D002118:Calcium / Q000097:blood*; D002121:Calcium Channel Blockers / Q000494:pharmacology; D002784:Cholesterol / Q000031:analogs & derivatives / Q000494:pharmacology*; D004912:Erythrocytes / Q000187:drug effects / Q000378:metabolism*; D006801:Humans; D007473:Ion Channels / Q000187:drug effects / Q000378:metabolism*; D007700:Kinetics; D008968:Molecular Conformation; D009543:Nifedipine / Q000031:analogs & derivatives / Q000494:pharmacology; D009568:Nitrendipine
chemical_list: D002121:Calcium Channel Blockers; D007473:Ion Channels; D002784:Cholesterol; D009568:Nitrendipine; D009543:Nifedipine; D002118:Calcium