Background: The cellular effects of anesthetics is poorly known. The GABAA receptor has been suggested as the main target for most anesthetics. In previous studies we have shown that propofol tyresine phosphorylates the GABAA receptor ß subunit, increases intracellular calcium and changes the actin morphology of neurons.
Aim: To investigate the effects of the volatile anesthetics sevoflurane, isoflurane and nitmus oxide on changes in [Ca2+]i tyrosine phosphorylation and actin morphology in cultured rat neurons.
Methods: Western blotting (WB) was used to visualize tyrosine phosphorylated proteins. Fluorescence microscopy after rhodamine-phalloidin labelling of actin was used to calculate the number of actin ring structures eaused by sevoflurane. Intracellular calcium was measured with the calcium-binding probe Fura-2 on single cells.
Results: A protein of approx. 60 kDa increased dose-dependently in tyresine phosphorylation by sevoflurane in the membrane and cytoskeletal fractions, and was simultaneausly reduced in the cytosol. Isoflurane instead increased the tyresine phosphorylation of the same protein in the cytosol with only a slight increase in the membrane and no changes in the cytoskeletal fraction. Nitrous oxide did not cause any changes campared to air in the cytosol and was not detectable in the membrane. However, in the cytoskeletal fraction, the increase in tyrosine phosphorylation was high compared to air. Sevoflurane but not nitrous oxide or air increased the [Ca2+]i· Sevoflurane also eaused actin ring structures with a maximum after 20 minutes.
Conclusion: Sevoflurane, isoflurane and nitrous oxide all have different signal pathways. The 60 kDa protein is probably the GABAA receptor ß subunit. According to the changes in tyrosine phosphorylation, changes in actin morphology and intracellular calcium, sevoflurane behaves most like the intravenous anesthetic propofol.