title: Halothane and isoflurane augment depolarization-induced cytosolic CA2+ transients and attenuate carbachol-stimulated CA2+ transients.
abstract: BACKGROUND
  Neuronal excitability is in part determined by Ca2+ availability that is controlled by regulatory mechanisms of cytosolic Ca2+ ([Ca2+]cyt). Alteration of any of those mechanisms by volatile anesthetics (VAs) may lead to a change in presynaptic transmission and postsynaptic excitability. Using a human neuroblastoma cell line, the effects of halothane and isoflurane on cytosolic Ca2+ concentration ([Ca2+]cyt) in response to K+ and carbachol stimulation were investigated.
  
  
  METHODS
  Volatile anesthetic (0.05-1 mm) action on stimulated [Ca2+]cyt transients were monitored in suspensions of SH-SY5Y cells loaded with fura-2. Potassium chloride (KCl; 100 mm) was used to depolarize and activate Ca2+ entry through voltage-dependent calcium channels; 1 mm carbachol was used to activate muscarinic receptor-mediated inositol triphosphate (IP3)-dependent intracellular Ca2+ release. Sequential stimulations, KCl followed by carbachol and vice versa, were used to investigate interactions between intracellular Ca2+ stores.
  
  
  RESULTS
  Halothane and isoflurane in clinically relevant concentrations enhanced the K+-evoked [Ca2+]cyt transient whether intracellular Ca2+ stores were full or partially depleted. In contrast, halothane and isoflurane reduced the carbachol-evoked [Ca2+]cyt transient when the intracellular Ca2+ stores were full but had no effect when the Ca2+ stores were partially depleted by KCl stimulation.
  
  
  CONCLUSIONS
  Volatile anesthetics acted on sites that differently affect the K+- and carbachol-evoked [Ca2+]cyt transients. These data suggest the involvement of an intracellular Ca2+ translocation from the caffeine-sensitive Ca2+ store to the inositol triphosphate-sensitive Ca2+ store that was altered by halothane and isoflurane.
authors.affiliation: Department of Anesthesiology, The Hospital for Special Surgery, New York, New York 10021, USA.
authors.forename: F
authors.initials: F
authors.lastname: Xu
authors.forename: J
authors.initials: J
authors.lastname: Zhang
authors.forename: E
authors.initials: E
authors.lastname: Recio-Pinto
authors.forename: T J
authors.initials: TJ
authors.lastname: Blanck
mesh_terms: D018685:Anesthetics, Inhalation / Q000494:pharmacology*; D002118:Calcium / Q000378:metabolism / Q000502:physiology*; D002217:Carbachol / Q000037:antagonists & inhibitors* / Q000494:pharmacology; D003600:Cytosol / Q000187:drug effects / Q000378:metabolism*; D004558:Electric Stimulation; D004594:Electrophysiology; D005456:Fluorescent Dyes; D016257:Fura-2; D006221:Halothane / Q000494:pharmacology*; D006801:Humans; D007530:Isoflurane / Q000494:pharmacology*; D008564:Membrane Potentials / Q000187:drug effects / Q000502:physiology; D018721:Muscarinic Agonists / Q000494:pharmacology*; D011189:Potassium Chloride / Q000494:pharmacology; D014407:Tumor Cells, Cultured
chemical_list: D018685:Anesthetics, Inhalation; D005456:Fluorescent Dyes; D018721:Muscarinic Agonists; D011189:Potassium Chloride; D002217:Carbachol; D007530:Isoflurane; D002118:Calcium; D016257:Fura-2; D006221:Halothane