Anesthetic-induced alteration of Ca2+ homeostasis in neural cells: A temperature-sensitive process that is enhanced by blockade of plasma membrane Ca2+-ATPase isoforms

John J. Franks, Artur W. Wamil, Piotr K. Janicki, Jean Louis Horn, William T. Franks, Victoria E. Janson, Thomas C. Vanaman, Paul C. Brandt

Research output: Contribution to journalArticlepeer-review

28 Scopus citations


Background: Many inhalation anesthetics at clinically relevant concentrations inhibit plasma membrane Ca2+-adenosine triphosphatase (PMCA) ion pumping in brain synaptic membranes and in cultured cells of neural origin. In this study, the authors investigated the effect of inhalation anesthetics on cytosolic calcium homeostasis in cortical neurons maintained at physiologic and room temperatures and on cortical neurons and pheochromocytoma cells with antisense blockade of specific PMCA isoforms. Methods: Using Ca2+-specific confocal microfluorimetry, the anesthetic effects on Ca2+ dynamics were examined in mouse embryonic cortical neurons in association with ligand-stimulated Ca2+ influx. Studies were done at 21°C and 37°C. Mouse embryonic cortical neurons with oligodeoxyribonucleotide blockade of PMCA2 expression and transfected rat pheochromocytoma cells with blocked expression of PMCA1 were also examined. Results: Baseline and poststimulation peak cytosolic calcium concentrations ([Ca2+](i) were increased, and Ca2+ clearance was delayed in cells exposed at 37°C, but not at 21°C, to concentrations ≤l minimum alveolar concentration (MAC) equivalent of halothane, isoflurane, and sevoflurane. Neurons exposed to xenon solutions ≤0.4, 0.6, and 0.8 MAC showed dose- related perturbations of cytosolic Ca2+. Calcium dynamics were altered in neural cells with blocked PMCA isoform production, but at much lower halothane concentrations: 0.5 MAC for cortical neurons and 0.1 MAC for pheochromocytoma cells. Conclusions: By extruding Ca2+ through the plasma membrane, PMCA maintains resting neuronal [Ca2+]1 at low levels and clears physiologic loads of Ca2+ after influx through calcium channels. Inhalation anesthetics perturb this process and thus may interfere with neurotransmitter release, altering interneuronal signaling.

Original languageEnglish (US)
Pages (from-to)149-164
Number of pages16
Issue number1
StatePublished - Jul 1998

All Science Journal Classification (ASJC) codes

  • Anesthesiology and Pain Medicine


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