Sphingolipids regulate [ Mg 2 + ] 0 uptake and [ Mg 2 + ] i content in vascular smooth muscle cells : potential mechanisms and importance to membrane transport of Mg 2 +

Zheng T, Li W, Altura BT, Shah NC, Altura BMSphingolipids regulate [Mg2 +]0 uptake and [Mg2 +]; content in vascular smooth muscle cells: potential mechanisms and importance to membrane transport of Mg + . Am J Physiol Heart Circ Physiol 300: H486H492, 2011. First published November 26, 20 I 0; doi: 1 0.1152/ajpheart.00976.20 1 0.-Sphingolipids have a variety of important signaling roles in mammalian cells. We tested the hypothesis that certain sphingolipids and neutral sphingomyelinase (N-SMase) can regulate intracellular free magnesium ions ([Mg2 +];) in vascular smooth muscle (VSM) cells. Herein, we show that several sphingolipids, including Crceramide, C8-ceramide, C wceramide, and sphingosine, as well as N-SMase, have potent and direct effects on content and mobilization of [Mg +]; in primary cultured rat aortic smooth muscle cells. All of these sphingolipid molecules increase, rapidly, [Mg +]; in these vascular cells in a concentration-dependent manner. The increments of [Mg +];, induced by these agents, are derived from influx of extracellular Mg2 + and are extracellular Ca2 + concentration-dependent. Phospholipase C and Ca2 + /calmodulin/ Ca + -A TPase activity appear to be important in the sphingolipidinduced rises of [Mg + ];. Activation of certain PKC isozymes may also be required for sphingolipid-induced rises in [Mg2 +];. These novel results suggest that sphingolipids may be homeostatic regulators of extracellular Mg + concentration influx (and transport) and [Mg2 +]; content in vascular muscle cells.