Correspondence  |   December 1995
Propofol and Cellular Calcium Homeostasis
Article Information
Correspondence   |   December 1995
Propofol and Cellular Calcium Homeostasis
Anesthesiology 12 1995, Vol.83, No Pagination Specified. doi:
Anesthesiology 12 1995, Vol.83, No Pagination Specified. doi:
To the Editor:--In an interesting paper, Jensen et al. 1described the effects of propofol on the cytosolic-free calcium concentration ([Ca2+]i) and on the cytoskeletal organization in neurons and astrocytes. The authors concluded that propofol induces an increase in [Ca2+]iand therefore a change in the organization of actin filaments. A large part of the discussion concerned the mechanisms of this [Ca2+]iincrease. However, the authors did not provide a consistent explanation for their findings.
At least three processes are involved in [Ca2+]iregulation:(1) the transmembrane Calcium2+ influx through voltage-activated Calcium2+ channels, (2) the release of Calcium2+ from intracellular stores (e.g., mitochondria or endoplasmic reticulum), and (3) the clearance of cytosolic Calcium2+ by reuptake in the intracellular stores or extrusion in the extracellular medium. The authors found two components of the [Ca2+]iincrease: an increased influx of extracellular Calcium2+ and a release of Calcium sup 2+ from intracellular stores.
Propofol has been found to inhibit transmembrane Calcium2+ current in myocytes and neurons. 2-3Nevertheless, a nonspecific membrane-fluidizing effect could be involved in the extracellular Calcium sup 2+ influx. The most interesting point concerns the release of Calcium sup 2+ from intracellular stores. The authors cite the work of Eriksson on rat liver mitochondria. 4In this study, the author demonstrated that propofol could inhibit Calcium2+ release from mitochondria. 4This finding appears for Jensen et al. to be contradictory with their own results. We studied the effects of propofol on Calcium2+ transport in mitochondria. As previously reported by Eriksson in liver mitochondria, we have shown in heart mitochondria that propofol inhibits the permeability transition pore and the mitochondrial Calcium2+ release. 5At higher concentrations (> 100 micro Meter), an uncoupling effect of propofol can decrease the mitochondrial Calcium2+ uptake through the potential-dependent Calcium2+ uniport.
We think that these data and those of Eriksson do not contradict the results of Jensen et al. In their study, the increase in [Ca2+]iafter addition of propofol could be due to a release from another intracellular store like the endoplasmic reticulum. Recently, Hossain et al. 6reported that some anesthetics (halothane, isoflurane, octanol) increase [Ca2+]iby inducing a leak of Calcium2+ from IP3-sensitive stores (e.g., endoplasmic reticulum). In the case of propofol, it seems important to test the same hypothesis to explain the results of Jensen et al.
Francois Sztark, M.D., Assistant in Anesthesiology.
Francois Ichas, M.D., Research Fellow.
Jean-Pierre Mazat, Ph.D., Professor of Biochemistry.
Philippe Dabadie, M.D., Professor of Anesthesiology, Laboratoire d'Anesthesiologie (GRAF/DBM2), Universite Bordeaux II, 33076 Bordeaux Cedex, France.
Jensen AG, Lindroth M, Sjolander A, Eintrei C: Propofol induces changes in the cytosolic free calcium concentration and the cytoskeletal organization of cultured human glial cells and primary embryonic rat brain cells. ANESTHESIOLOGY 81:1220-1229, 1994.
Cook DJ, Housmans PR: Mechanism of the negative inotropic effect of propofol in isolated ferret ventricular myocardium. ANESTHESIOLOGY 80:859-871, 1994.
Olcese R, Usai C, Maestrone E, Nobile M: The general anesthetic propofol inhibits transmembrane calcium current in chick sensory neurons. Anesth Analg 78:955-960, 1994.
Eriksson O: Effects of the general anaesthetic propofol on the calcium-induced permeabilization of rat liver mitochondria. FEBS Lett 279:45-49, 1991.
Sztark F, Ichas F, Ouhabi R, Dabadie P, Mazat JP: Effects of the anaesthetic propofol on the calcium-induced permeability transition of rat heart mitochondria: Direct pore inhibition and shift of the gating potential. FEBS Lett 368:101-104, 1995.
Hossain MD, Evers AS: Volatile anesthetic-induced efflux of calcium from IP sub 3 -gated stores in clonal (GH sub 3) pituitary cells. ANESTHESIOLOGY 80:1379-1389, 1994.