The cholesterol content of the human erythrocyte influences calcium influx through the channel.
In order to study the influence of the cholesterol content on the calcium entry channel, the human red blood cell was used as a model system. The cholesterol to lecithin ratio (C/L ratio) of the membrane was modified experimentally by incubating the cells (15h, 25 degrees) with liposomes of defined C/L ratios. Subsequently, net 45Calcium-influx into the cell was measured by inhibiting the Ca-ejecting ATPase with vanadate. Additionally, the use of nitrendipine, a potent calcium channel inhibitor, during incubation allowed the determination of Ca-influx through the calcium channel. A positive correlation between the 45Ca++-influx and the molar C/L ratio of the membrane was found over a wide C/L range. A molar C/L ratio of 1.4 in the membrane increased calcium influx by 150 % compared to controls (molar C/L ratio = 0.8, calcium influx rate = 100 %), while a molar C/L ratio at less than 0.75 decreased calcium influx by 50 %. We conclude, that the cholesterol content of the membrane greatly influences the calcium channel and thus plays a pivotal role for the availability of calcium as a second messenger. These findings may provide a link between high plasma cholesterol and the development of atherosclerosis as well as enhanced platelet aggregability.
D002118:Calcium / Q000097:blood*; D002784:Cholesterol / Q000097:blood*; D004912:Erythrocytes / Q000032:analysis*; D006801:Humans; D007473:Ion Channels / Q000378:metabolism*; D007700:Kinetics; D008081:Liposomes / Q000378:metabolism; D009543:Nifedipine / Q000031:analogs & derivatives / Q000494:pharmacology; D009568:Nitrendipine; D010713:Phosphatidylcholines / Q000097:blood; D013997:Time Factors
D007473:Ion Channels; D008081:Liposomes; D010713:Phosphatidylcholines; D002784:Cholesterol; D009568:Nitrendipine; D009543:Nifedipine; D002118:Calcium