Effects of propofol on intracellular Ca2+ homeostasis in human astrocytoma cells.
The effects of propofol, a short-acting general anesthetic, upon cell growth and Ca(2+) 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 microM. To evaluate the changes in intracellular Ca(2+) homeostasis induced by propofol, cytoplasmic and mitochondrial Ca(2+) were measured by fluorescence imaging. Mitochondrial Ca(2+) increased while cytoplasmic Ca(2+) decreased significantly at a propofol concentration lower than the IC50 (10 microM for 24 h, 1 microM for 72 h). In addition, propofol diminished the Ca(2+) response induced by fetal bovine serum (FBS). To determine the source of Ca(2+) alterations induced by propofol, pharmacologic agents targeting intracellular Ca(2+) homeostasis mechanisms were used. Nifedipine, an L-type Ca(2+) channel blocker, decreased FBS-induced Ca(2+) 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 Ca(2+) in control cells to a level comparable to propofol treated cells suggesting activation of these channels by propofol treatment. Addition of 1 muM RU-360 (a selective blocker of the mitochondrial Ca(2+) uniporter) for 30 min prior to propofol treatment restored mitochondrial and cytoplasmic Ca(2+) to control levels. These data suggest that voltage operated Ca(2+) channels, mitochondrial Ca(2+) and K(+)-ATP channels may be targets of propofol action in astrocytes.
Barhoumi
Rola
R
Department of Veterinary Integrative Biosciences, Texas A&M University, College Station, TX 77843-4458, USA. rmouneimne@cvm.tamu.edu
Burghardt
Robert C
RC
Qian
Yongchang
Y
Tiffany-Castiglioni
Evelyn
E
D018686:Anesthetics, Intravenous / Q000494:pharmacology; D001253:Astrocytes / Q000187:drug effects* / Q000378:metabolism; D001921:Brain / Q000187:drug effects* / Q000378:metabolism; D002118:Calcium / Q000378:metabolism*; D002120:Calcium Channel Agonists / Q000494:pharmacology; D002121:Calcium Channel Blockers / Q000494:pharmacology; D015220:Calcium Channels / Q000187:drug effects / Q000378:metabolism; D020013:Calcium Signaling / Q000187:drug effects* / Q000502:physiology; D016923:Cell Death / Q000187:drug effects / Q000502:physiology; D045744:Cell Line, Tumor; D003600:Cytosol / Q000187:drug effects / Q000378:metabolism; D004305:Dose-Response Relationship, Drug; D006706:Homeostasis / Q000187:drug effects / Q000502:physiology; D006801:Humans; D007424:Intracellular Fluid / Q000187:drug effects / Q000378:metabolism; D008928:Mitochondria / Q000187:drug effects / Q000378:metabolism; D015221:Potassium Channels / Q000187:drug effects / Q000378:metabolism; D015742:Propofol / Q000494:pharmacology*
D018686:Anesthetics, Intravenous; D002120:Calcium Channel Agonists; D002121:Calcium Channel Blockers; D015220:Calcium Channels; D015221:Potassium Channels; C117780:mitochondrial K(ATP) channel; D002118:Calcium; D015742:Propofol