Xue Gao, Xiu Wang , Lei Zhang , Ge Liang , Rachel Mund and Huafeng Wei * Pages 1311 - 1319 ( 9 )
<P>Background: We have hypothesized that the most commonly used intravenous (propofol) and inhalational (sevoflurane) general anesthetics affect cell survival concentration and duration dependently with different potency associated with their differential potency to affect intracellular Ca+2 homeostasis. </P><P> Methods: Human neuroblastoma SH-SY5Y cells stably transfected with either wild type or M146L mutant human presenilin 1 were cultured and exposed to equipotent of propofol or sevoflurane. Cell viability, cytosolic and mitochondrial calcium were measured. </P><P> Results: Sevoflurane but not propofol, at clinically relevant concentrations and durations, promoted cell survival. Prolonged exposure (24 hours) of 1% sevoflurane resulted in significant cell damage in both types of cells. Both sevoflurane and propofol had significantly higher cell response rates to the elevation of cytosolic Ca<sup>+2</sup> or mitochondrial Ca<sup>+2</sup> in the presence of extracellular calcium. With the contribution of Ca<sup>+2</sup> influx, sevoflurane but not equipotent 1 MAC propofol, caused a significantly greater increase in peak and overall Ca<sup>+2</sup> in Alzheimer’s mutation cell than in wild type cells, but significantly more increase in overall mitochondrial Ca<sup>+2</sup> concentrations in wild type than mutation cells. In the absence of extracellular Ca<sup>+2</sup> influx, sevoflurane, but not propofol, caused more significant elevations of overall mitochondrial Ca<sup>+2</sup> concentration in mutation cells than control cells. </P><P> Conclusion: Calcium influx contributed to the general anesthetics mediated elevation of cytosolic or mitochondrial Ca<sup>+2</sup>, which is especially true for propofol. Sevoflurane has a greater potency to either promote or inhibit cell survival than propofol, which may be associated with its ability to affect cytosolic or mitochondrial Ca<sup>+2</sup> concentrations.</P>
Anesthetics, Alzheimer's disease, calcium, neurodegeneration, apoptosis, cell death.
Department of Anesthesiology and Critical Care, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA 19104, Department of Anesthesiology and Critical Care, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA 19104, Department of Anesthesiology and Critical Care, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA 19104, Department of Anesthesiology and Critical Care, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA 19104, Department of Anesthesiology and Critical Care, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA 19104, Department of Anesthesiology and Critical Care, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA 19104