Cholesterol modulates activity of calcium-dependent ATPase of the sarcoplasmic reticulum

Abstract

BIOMEMBRANES consist of an asymmetric lipid bilayer matrix into which and around which the various proteins are situated. The proteins may be attached to the outside of the lipid bilayer (extrinsic proteins), but in many cases the proteins (intrinsic proteins) are embedded within, and can span, the bilayer. Associated with this is the idea that in many cases the lipid matrix is in a fluid condition in which the lipids are essentially above their transition temperature (T_c) and able to diffuse along the bilayer length. The perturbation introduced into the lipid bilayer by the presence of an intrinsic protein has recently been discussed^2,3. Some workers^4,5 have suggested that intrinsic proteins, for example the Ca²⁺-ATPase of the sarcoplasmic reticulum, carry with them, even when excess bulk fluid lipid occurs, a shell of immobilised lipid, referred to as an annulus, which controls the enzyme activity. The shell is said to exclude cholesterol so that cholesterol molecules do not influence the enzyme activity. We report here the use of cholesterol-enriched liposomes to reversibly vary the content of cholesterol in the sarcoplasmic membranes. We show in contrast to the previous work that as the cholesterol content of the membrane varies so does the activity of the Ca²⁺-ATPase.