Organotypic Cultures of Spinal Cord Ventral Horn Are Valuable Tools for Investigating Immobility-Related Mechanisms In Vitro

Abstract

To the Editor: Using decerebrated rats, Kungys et al.1 identified the ventral horn of the spinal cord as the pivotal region within the spinal cord where propofol induces immobility. Their finding that the effects of propofol but not isoflurane were antagonized by picrotoxin indicates that only propofol acts predominantly via GABA(A) receptors. In the discussion, Kungys et al. argue that spinal slice cultures, which have been used in our work, are not well suited for the study of anesthetic mechanisms because of artificial receptor expression during ex vivo development. Moreover, the authors imply that their observations are inconsistent with results published by our group,2 stating erroneously that in our study propofol acted via glycine and GABAA receptors. To the contrary, we reported that propofol acted almost exclusively via GABA(A) receptors, which is clearly consistent with the findings of Kungys et al. Moreover, we showed that in spinal cord slice cultures, GABA(A) receptors are only a minor target for isoflurane.3 Again, this observation agrees with the results reported by Kungys et al. In cultured spinal slices, propofol showed a limited efficacy to depress ventral horn network activity compared with isoflurane, which is consistent with the findings of Kungys et al. and also in good agreement with clinical studies.4,5 Finally, we showed that beta3 subunit-containing GABA(A) receptors are essential for mediating the immobilizing actions of etomidate in mice and the actions of the same anesthetic in cultured spinal slices.6 In our opinion, in vivo and in vitro data on the spinal actions of general anesthetics are in excellent accord with each other and provide impressive evidence of the mechanisms and neural substrates by which anesthetics produce immobility. Christian Grasshoff, MD Bernd Antkowiak, PhD Department of Anesthesiology and Intensive Care Experimental Anesthesiology Section Eberhard-Karls-University Tuebingen, Germany [email protected]