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Positive modulation of human gamma-aminobutyric acid type A and glycine receptors by the inhalation anesthetic isoflurane.
Abstract
The interactions of the inhalation anesthetic agent isoflurane with ligand-gated chloride channels were studied using transient expression of recombinant human receptors in a mammalian cell line. Isoflurane enhanced gamma-aminobutyric acid (GABA)-activated chloride currents in cells that expressed heteromeric GABAA receptors consisting of combinations of alpha 1 or alpha 2, beta 1, and gamma 2 subunits and in cells that expressed receptors consisting of combinations of only alpha and beta subunits. Receptors consisting of alpha 2 and gamma 2 subunits were poorly expressed but were sensitive to isoflurane. Receptors consisting of beta 1 and gamma 2 subunits were not expressed. Isoflurane also enhanced glycine-activated chloride currents through homomeric alpha glycine receptors but did not enhance GABA currents in cells expressing homomeric rho 1 receptors. These results show that not all ligand-gated chloride channel receptors are sensitive to isoflurane and, therefore, that the anesthetic interacts with specific structural determinants of these ion channel proteins.
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Citations
Cited by
General anaesthesia: from molecular targets to neuronal pathways of sleep and arousal
Franks, N. P. (2008) · Nature Reviews Neuroscience · doi:10.1038/nrn2372 · Cited by 1,295
Molecular Structure and Physiological Function of Chloride Channels
Jentsch, T. J., Stein, V., Weinreich, F., & Zdebik, A. A. (2002) · Physiological Reviews · doi:10.1152/physrev.00029.2001 · Cited by 1,256
Sites of alcohol and volatile anaesthetic action on GABAA and glycine receptors
Mihic, S. J., Ye, Q., Wick, M. J., Koltchine, V. V., Krasowski, M. D., Finn, S. E., Mascia, M. P., Valenzuela, C. F., Hanson, K. K., Greenblatt, E. P., et al. (1997) · Nature · doi:10.1038/38738 · Cited by 1,219
Self-citationGeneral anaesthetic actions on ligand-gated ion channels
Krasowski, M. D., & Harrison, N. L. (1999) · Cellular and Molecular Life Sciences (CMLS) · doi:10.1007/s000180050371 · Cited by 384
Self-citationJonckers, E., Delgado y Palacios, R., Shah, D., Guglielmetti, C., Verhoye, M., & Van der Linden, A. (2014) · Magnetic Resonance in Medicine · doi:10.1002/mrm.24990 · Cited by 155
Metadata
- Authors
- Harrison, N. L., Kugler, J. L., Jones, M. V., Greenblatt, E. P., & Pritchett, D. B.
- Venue
- Molecular Pharmacology
- Publisher
- Elsevier BV
- Published
- 1993-09
- Volume
- 44
- Issue
- 3
- Pages
- 628-632
- ISSN
- 0026-895X (ISSN-L)
- OpenAlex
- W2342124397
- Cited by
- 167
- References
- 0
- FWCI
- 2.18
- Type
- journal article
- Language
- en
- Open access
- closed
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- CoChat. (2026). Citation check: Positive modulation of human gamma-aminobutyric acid type A and glycine receptors by the inhalation anesthetic isoflurane. https://app.cochat.ai/papers/10.1016/s0026-895x(25)13234-3
- The paper
- Harrison, N. L., Kugler, J. L., Jones, M. V., Greenblatt, E. P., & Pritchett, D. B. (1993). Positive modulation of human gamma-aminobutyric acid type A and glycine receptors by the inhalation anesthetic isoflurane. Molecular Pharmacology. https://doi.org/10.1016/s0026-895x(25)13234-3
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Contains information from the Semantic Scholar Academic Graph Datasets, made available under the ODC Attribution License (ODC-BY 1.0).
Semantic Scholar’s data is described in: Kinney, R., et al. (2023). The Semantic Scholar Open Data Platform. arXiv:2301.10140.
