The effects of midazolam and sevoflurane on the GABA receptors with alternatively spliced variants of the γ2 subunit
BackgroundEmergence agitation after sevoflurane anesthesia in children can be prevented by midazolam. Alternative splicing of the GABAA receptor changes with age. Therefore, we hypothesized that alternative splicing of the γ2 subunit affects the GABA current when applying sevoflurane and midazolam.M...
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Korean Society of Anesthesiologists
2011-02-01
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| Series: | Korean Journal of Anesthesiology |
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| Online Access: | http://ekja.org/upload/pdf/kjae-60-109.pdf |
| _version_ | 1829484399823945728 |
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| author | Woosik Eom Jung Min Lee Jeongmi Park Kyungho Choi Sung-Jun Jung Hee-Soo Kim |
| author_facet | Woosik Eom Jung Min Lee Jeongmi Park Kyungho Choi Sung-Jun Jung Hee-Soo Kim |
| author_sort | Woosik Eom |
| collection | DOAJ |
| description | BackgroundEmergence agitation after sevoflurane anesthesia in children can be prevented by midazolam. Alternative splicing of the GABAA receptor changes with age. Therefore, we hypothesized that alternative splicing of the γ2 subunit affects the GABA current when applying sevoflurane and midazolam.MethodsWe performed the whole-cell patch clamp technique on human embryonic kidney 293 cells that were transfected with α1β2γ2L or α1β2γ2S. The concentration-response relations were recorded for midazolam and sevoflurane, and the co-application responses were measured at concentrations of 1.5 nM, 15 nM and 300 nM of midazolam and 0.5%, 2.0% and 4.0% of sevoflurane. Each GABA current was compared with that produced by 5 µM of GABA.ResultsThe concentration-response relationships for midazolam and sevoflurane were dose-dependent without any differences between the α1β2γ2L and α1β2γ2S subtypes. 1.5 nM and 15 nM of midazolam did not significantly enhance the current after treatment with 0.5% sevoflurane for both subtypes. The current after treatment with 2.0% sevoflurane was enhanced by 1.5 nM midazolam for the α1β2γ2S subtype, but not for the α1β2γ2L subtype. In the case of 2.0% sevoflurane with 15 nM of midazolam, and 4.0% sevoflurane with 300 nM of midazolam, the GABA currents were significantly enhanced for both subtypes.ConclusionsThese results show that the difference in the γ2 subunit cannot explain the emergence agitation after sevoflurane anesthesia in children in vitro. This suggests that co-application of sevoflurane and midazolam enhances the GABA current according to the alternative splicing of the γ2 subunit and the concentration of both drugs. |
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| institution | Directory Open Access Journal |
| issn | 2005-6419 2005-7563 |
| language | English |
| last_indexed | 2024-12-14T22:26:05Z |
| publishDate | 2011-02-01 |
| publisher | Korean Society of Anesthesiologists |
| record_format | Article |
| series | Korean Journal of Anesthesiology |
| spelling | doaj.art-4f460617e70f4d28826e3b1d70289d032022-12-21T22:45:22ZengKorean Society of AnesthesiologistsKorean Journal of Anesthesiology2005-64192005-75632011-02-0160210911810.4097/kjae.2011.60.2.1097074The effects of midazolam and sevoflurane on the GABA receptors with alternatively spliced variants of the γ2 subunitWoosik Eom0Jung Min Lee1Jeongmi Park2Kyungho Choi3Sung-Jun Jung4Hee-Soo Kim5Department of Anesthesiology and Pain Medicine, National Cancer Center, Goyang, Korea.Department of Anesthesiology and Pain Medicine, Seoul National University Hospital, Seoul National University College of Medicine, Seoul, Korea.Department of Anesthesiology and Pain Medicine, Seoul National University Hospital, Seoul National University College of Medicine, Seoul, Korea.Specific Organs Cancer Branch, Research Institute, National Cancer Center, Goyang, Korea.Department of Physiology, Hanyang University College of Medicine, Seoul, Korea.Department of Anesthesiology and Pain Medicine, Seoul National University Hospital, Seoul National University College of Medicine, Seoul, Korea.BackgroundEmergence agitation after sevoflurane anesthesia in children can be prevented by midazolam. Alternative splicing of the GABAA receptor changes with age. Therefore, we hypothesized that alternative splicing of the γ2 subunit affects the GABA current when applying sevoflurane and midazolam.MethodsWe performed the whole-cell patch clamp technique on human embryonic kidney 293 cells that were transfected with α1β2γ2L or α1β2γ2S. The concentration-response relations were recorded for midazolam and sevoflurane, and the co-application responses were measured at concentrations of 1.5 nM, 15 nM and 300 nM of midazolam and 0.5%, 2.0% and 4.0% of sevoflurane. Each GABA current was compared with that produced by 5 µM of GABA.ResultsThe concentration-response relationships for midazolam and sevoflurane were dose-dependent without any differences between the α1β2γ2L and α1β2γ2S subtypes. 1.5 nM and 15 nM of midazolam did not significantly enhance the current after treatment with 0.5% sevoflurane for both subtypes. The current after treatment with 2.0% sevoflurane was enhanced by 1.5 nM midazolam for the α1β2γ2S subtype, but not for the α1β2γ2L subtype. In the case of 2.0% sevoflurane with 15 nM of midazolam, and 4.0% sevoflurane with 300 nM of midazolam, the GABA currents were significantly enhanced for both subtypes.ConclusionsThese results show that the difference in the γ2 subunit cannot explain the emergence agitation after sevoflurane anesthesia in children in vitro. This suggests that co-application of sevoflurane and midazolam enhances the GABA current according to the alternative splicing of the γ2 subunit and the concentration of both drugs.http://ekja.org/upload/pdf/kjae-60-109.pdfagitationalternative splicinggaba receptorgamma 2 subunitmidazolamsevoflurane |
| spellingShingle | Woosik Eom Jung Min Lee Jeongmi Park Kyungho Choi Sung-Jun Jung Hee-Soo Kim The effects of midazolam and sevoflurane on the GABA receptors with alternatively spliced variants of the γ2 subunit Korean Journal of Anesthesiology agitation alternative splicing gaba receptor gamma 2 subunit midazolam sevoflurane |
| title | The effects of midazolam and sevoflurane on the GABA receptors with alternatively spliced variants of the γ2 subunit |
| title_full | The effects of midazolam and sevoflurane on the GABA receptors with alternatively spliced variants of the γ2 subunit |
| title_fullStr | The effects of midazolam and sevoflurane on the GABA receptors with alternatively spliced variants of the γ2 subunit |
| title_full_unstemmed | The effects of midazolam and sevoflurane on the GABA receptors with alternatively spliced variants of the γ2 subunit |
| title_short | The effects of midazolam and sevoflurane on the GABA receptors with alternatively spliced variants of the γ2 subunit |
| title_sort | effects of midazolam and sevoflurane on the gaba receptors with alternatively spliced variants of the γ2 subunit |
| topic | agitation alternative splicing gaba receptor gamma 2 subunit midazolam sevoflurane |
| url | http://ekja.org/upload/pdf/kjae-60-109.pdf |
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