Effects of propofol on intracellular Ca2+ homeostasis in human astrocytoma cells

The effects of propofol, a short-acting general anesthetic, upon cell growth and Ca2+ signaling in a human astrocytic cell line were examined. Exposure of cells to graded concentrations of propofol resulted in a dose-dependent decrease in cell number with an inhibitory concentration of cell viability (IC50) of 31.7 +/- 1.2 mu M. To evaluate the changes in intracellular Ca2+ homeostasis induced by propofol, cytoplasmic and mitochondrial Ca2+, were measured by fluorescence imaging. Mitochondrial Ca2+, increased while cytoplasmic Ca2+ decreased significantly at a propofol concentration lower than the IC50 (10 mu M for 24 h, 1 mu M for 72 h). In addition, propofol diminished the Ca2+ response induced by fetal bovine serum (FBS). To determine the source of Ca2+ alterations induced by propofol, pharmacologic agents targeting intracellular Ca2+ homeostasis mechanisms were used. Nifedipine, an L-type Ca2+ channel blocker, decreased FBS-induced Ca2+ response of control cells to a level similar to propofol treated cells. However, diazoxide (a K+-ATP channel opener) administered 1 h before FBS addition restored the FBS response in propofol treated cells to a level similar to control. In addition, diazoxide increased mitochondrial Ca2+, in control cells to a level comparable to propofol treated cells suggesting activation of these channels by propofol treatment. Addition of 1 mu M RU-360 (a selective blocker of the mitochondrial Ca2+ uniporter) for 30 min prior to propofol treatment restored mitochondrial and cytoplasmic Ca2+, to control levels. These data suggest that voltage operated Ca2+, channels, mitochondrial Ca2+ and K+-ATP channels may be targets of propofol action in astrocytes. (c) 2007 Elsevier B.V. All rights reserved.