REGULATION OF RABBIT ERYTHROCYTE CA2-PUMP SENSITIVITY TO CALMODULIN IN EXPERIMENTAL HYPERLIPIDEMIA()

Intracellular free calcium activity Is in part determined by a calmodu lin-regulated plasma membrane Ca2+-pump. Since changes in Ca2+ permeab ility have been implicated In atherosclerotic plaque formation, we ini tiated a lipid hyperallmentation protocol during which we measured var ious erythrocyte calcium flux parameters and early atheroma developmen t. Adolescent New Zealand White rabbits were fed a diet with 0.5% chol esterol and 2.5% lard over a 3-month period. Plasma cholesterol and tr iacylglycerols increased an average 18.7- and 13.9-fold respectively, while erythrocyte membrane cholesterol content decreased 18% and total phospholipids by 54%. After 3 months of lipid hyperalimentation, 22% of the aortic arch was covered with large, early-stage, raised atherom a. Basal and calmodulin-activated (Ca2+ + Mg2+)-ATPase activities in e rythrocyte membranes increased by 31% and 123%, respectively at 2 mont hs, with a concomitant increase in calmodulin affinity (K-m) from 15.6 to 4.2 nM. These differences were transient on account of changes in the control animals which exhibited a slowly developing sensitivity to calmodulin during maturation. Basal Ca2+ transport and passive Ca2+ p ermeability increased about 7-fold during the hyperlipidemic phase. Th is suggests that overt hyperlipidemia, leading to atherosclerotic plaq ue development, alters plasma membrane Ca2+ regulatory mechanisms incl uding passive Ca2+ permeability. The changes in enzymatic function, me mbrane composition, and Ca2+ permeability seen in this red cell model system may be a reflection of early changes in cells that are directly involved in the development of atherosclerotic plaques.