KMID : 0356920110600020109
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Korean Journal of Anesthesiology 2011 Volume.60 No. 2 p.109 ~ p.118
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The effects of midazolam and sevoflurane on the GABAA receptors with alternatively spliced variants of the ¥ã2 subunit
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Eom Woo-Sik
Lee Jung-Min Park Jeong-Mi Choi Kyung-Ho Jung Sung-Jun Kim Hee-Soo
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Abstract
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Background:Emergence 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 ¥ã2 subunit affects the GABA current when applying sevoflurane and midazolam.
Methods: We performed the whole-cell patch clamp technique on human embryonic kidney 293 cells that were transfected with ¥á1¥â2¥ã2L or ¥á1¥â2¥ã2S. 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 ¥ìM of GABA.
Results: The concentration-response relationships for midazolam and sevoflurane were dose-dependent without any differences between the ¥á1¥â2¥ã2L and ¥á1¥â2¥ã2S 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 ¥á1¥â2¥ã2S subtype, but not for the ¥á1¥â2¥ã2L 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.
Conclusions: These results show that the difference in the ¥ã2 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 ¥ã2 subunit and the concentration of both drugs.
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KEYWORD
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Agitation, Alternative splicing, GABAA receptor, Gamma 2 subunit, Midazolam, Sevoflurane
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