Mg²⁺ modulates membrane sphingolipid and lipid second messenger levels in vascular smooth muscle cells

Abstract

In vitro studies with smooth muscle cells from rat aorta and dog cerebral blood vessels indicate that variation in free Mg2+, within the pathophysiological range of Mg2+ concentrations, found in human serum, causes sustained changes in membrane phospholipids and lipid second messengers. Incorporation of [3H]palmitic acid into phosphatidylcholine (PC) and sphingomyelin (SM) was altered within 15-30 min after modifying the extracellular Mg2+ ion level ([Mg2+]o). Decreased Mg2+ produced a fall in both [3H]SM and [3H]PC over the first 2 h. After an 18-h incubation, the [3H]PC/[3H]SM ratio changed from about 20:1 to about 50:1. Increased [Mg2+]o resulted in a 2- to 3-fold increase in [3H]SM compared to only a small increase in [3H]PC over the same period. There was a reciprocal relationship between [3H]ceramide and [3H]1,2-DAG levels with highest [3H]ceramide and lowest [3H]-1,2-DAG levels seen at lowest [Mg2+]o. The results indicate that a fall in extracellular ionized Mg2+ concentration produces a rapid and sustained decrease in membrane sphingomyelin and a moderate rise in intracellular ceramide. A major effect of lowering [Mg2+]o appears to be a down-regulation of SM synthase. The increased membrane SM content and a concomitant decrease in cell ceramide, in the presence of elevated [Mg2+]o, may be relevant to the apparent protective role of adequate Mg intake on vascular function in humans.