Effects of Propofol on the Cytosolic Calcium Concentration of the Astrocytoma Cells

Abstract

Background: Propofol is a widely-used intravenous anesthetic with a rapid onset, short duration of action and rapid elimination but the molecular mechanisms of action are not completely understood. Not only neurons but astrocytes are potential substrates for anesthetics, specifically for propofol. Intracellular calcium ion ([Ca2+]) is known to play a key role in the transduction and propagation of various chemical signals in astrocytes. Methods: In the present study, the effects of propofol on the intracellular calcium concentration of astrocytoma cells by using a fura-2 fluorescence spectroscopy was investigated. Results: In an isotonic standard solution, propofol (50 and 500 μM) produced a transient increase in [Ca2+]; while the intralipid did not change [Ca2+];. In several cells (20%), a transient increase in [Ca2+]; was followed by sustained elevation which was sensitive to depletion of external calcium. A propofol-induced increase in [Ca2+]; was not altered by an L-type calcium channel blocker (nifedipine 2μM). In cells bathed in a Ca2+ree external solution, a transient increase in [Ca2+ was observed. After the pretreatment of cyclopiazonic acid (CPA), an endoplasmic reticulum Ca2+-ATPase blocker, propofol 500 μM did not produce any significant increase in [Ca2+];. Carbachol, which is known to release calcium from the inositol 1,4,5-triphosphate (IP3)-induced calcium release (IICR) stores, prevented the [Ca2+]; increase by propofol and vice versa. High concentrations of caffeine (10 mM), which release calcium from the calcium-induced calcium release (CICR) stores, had no effect on [Ca2+]. Conclusions: From the above results, it is suggested that an increase in [Ca2+]; by propofol in astrocytoma cells is mainly due to calcium release from the IICR stores. (Korean J Anesthesiol 2001; 41: 337-346)