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High density lipoproteins--modulators of the calcium channel?
Insights
High-density lipoproteins (HDL) inversely correlate with calcium influx in red blood cells, suggesting a link between plasma lipids and cellular calcium regulation in diseases like atherosclerosis.
Area of Science:
- Cardiovascular Science
- Cellular Physiology
- Lipid Metabolism
Background:
- Human red blood cells have a voltage-independent calcium channel.
- In vitro studies show membrane cholesterol affects this channel.
- In vivo relevance of plasma lipids to this channel is unknown.
Purpose of the Study:
- To investigate the relationship between plasma lipids and calcium influx through the red blood cell calcium channel under in vivo conditions.
Main Methods:
- Measured 45Ca2+ influx in red blood cells from 51 male donors.
- Defined channel influx as nitrendipine-inhibitable 45Ca2+ influx.
- Inhibited Ca(2+)-ejecting ATPase with vanadate.
Main Results:
- A strong inverse relationship was observed between plasma high-density lipoprotein (HDL) concentration and 45Ca2+ influx (r = -0.81; P < 0.001).
- No significant correlation was found with triglycerides, LDL, VLDL, total cholesterol, or electrolytes.
- This suggests HDL modulates the calcium channel activity.
Conclusions:
- Plasma HDL levels are inversely associated with calcium influx in red blood cells.
- HDL plays a role in modulating this calcium channel.
- Provides a link between cholesterol turnover, calcium influx, and pathogenesis of atherosclerosis and hypertension.
Abstract:
It has recently been shown that human red blood cells possess a voltage-independent calcium channel which can be influenced by in vitro modification of the membraneous cholesterol content. To determine whether there is also a link between plasma lipids and the calcium influx through this channel under in vivo conditions, the calcium influx was measured in red blood cells from 51 male donors (aged 41 +/- 5 years). The influx through the channel was defined as the nitrendipine (15 mumol/l)-inhibitable part of 45Ca2+ influx. The Ca(2+)-ejecting ATPase was inhibited by vanadate. The results demonstrate a strong inverse relationship (r = -0.81; P < 0.001) between the plasma concentration of high density lipoproteins (HDL) and 45Ca2+ influx. No significant correlation was found between 45Ca2+ influx and triglycerides, low density lipoproteins (LDL), very low density lipoproteins (VLDL), total plasma cholesterol or extracellular electrolytes (K+, Na+, Ca2+, Mg2+). The results indicate that HDL are involved in the modulation of the calcium channel and provide a link between the cellular cholesterol turnover and the calcium influx in the pathogenesis of atherosclerosis and hypertension.