Effects of tranexamic acid on the activity of glutamate transporter EAAT3
Background Tranexamic acid (TXA) is the most widely used hemostatic agent in surgical patients. However, when used in a high dose, it could cause a seizure in the postoperative period. The exact effector mechanism behind the seizure triggering remains unknown. Therefore, the authors investigated the...
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| Format: | Article |
| Language: | English |
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Korean Society of Anesthesiologists
2020-07-01
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| Series: | Anesthesia and Pain Medicine |
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| Online Access: | http://www.anesth-pain-med.org/upload/pdf/apm-20004.pdf |
| _version_ | 1797825484215549952 |
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| author | Hyun-Jung Shin Soo-Young Lee Hyo-Seok Na Bon-Wook Koo Jung-Hee Ryu Sang-Hwan Do |
| author_facet | Hyun-Jung Shin Soo-Young Lee Hyo-Seok Na Bon-Wook Koo Jung-Hee Ryu Sang-Hwan Do |
| author_sort | Hyun-Jung Shin |
| collection | DOAJ |
| description | Background Tranexamic acid (TXA) is the most widely used hemostatic agent in surgical patients. However, when used in a high dose, it could cause a seizure in the postoperative period. The exact effector mechanism behind the seizure triggering remains unknown. Therefore, the authors investigated the effects of TXA on the activity of glutamate transporter type 3 (excitatory amino acid transporter 3; EAAT3), which is the main neuronal glutamate transporter type. Methods EAAT3 was expressed in Xenopus laevis oocytes through mRNA injection. Oocytes were incubated with diluted tranexamic acid for 72 h. Two-electrode voltage clamping was used to measure membrane currents before, during, and after applying 30 µM L-glutamate. Responses were quantified by integrating the current traces and reported in microcoulombs (µC). Results were presented as mean ± SEM. Results TXA (30 to 1,000 µM) significantly decreased EAAT3 activity. Our kinetic study showed that Vmax was significantly decreased in the TXA group compared with the control group (1.1 ± 0.1 vs. 1.4 ± 0.1 µC, n = 18–23, P = 0.043), but the Km did not significantly change (12.7 ± 3.9 µM for TXA vs. 12.8 ± 3.8 for control, n = 18–23, P = 0.986). Conclusions Our results suggest that TXA attenuates EAAT3 activity, which may explain its proconvulsant effect. |
| first_indexed | 2024-03-13T10:54:39Z |
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| id | doaj.art-beb4c6b7c7ca4fecb538090849d1435d |
| institution | Directory Open Access Journal |
| issn | 1975-5171 2383-7977 |
| language | English |
| last_indexed | 2024-03-13T10:54:39Z |
| publishDate | 2020-07-01 |
| publisher | Korean Society of Anesthesiologists |
| record_format | Article |
| series | Anesthesia and Pain Medicine |
| spelling | doaj.art-beb4c6b7c7ca4fecb538090849d1435d2023-05-17T05:41:38ZengKorean Society of AnesthesiologistsAnesthesia and Pain Medicine1975-51712383-79772020-07-0115329129610.17085/apm.200041017Effects of tranexamic acid on the activity of glutamate transporter EAAT3Hyun-Jung Shin0Soo-Young Lee1Hyo-Seok Na2Bon-Wook Koo3Jung-Hee Ryu4Sang-Hwan Do5 Department of Anesthesiology and Pain Medicine, Seoul National University Bundang Hospital, Seongnam, Korea 2Department of Anesthesiology and Pain Medicine, ThanQ Seoul Thyroid-Head & Neck Surgery Center, Seoul, Korea Department of Anesthesiology and Pain Medicine, Seoul National University Bundang Hospital, Seongnam, Korea Department of Anesthesiology and Pain Medicine, Seoul National University Bundang Hospital, Seongnam, Korea Department of Anesthesiology and Pain Medicine, Seoul National University Bundang Hospital, Seongnam, Korea Department of Anesthesiology and Pain Medicine, Seoul National University Bundang Hospital, Seongnam, KoreaBackground Tranexamic acid (TXA) is the most widely used hemostatic agent in surgical patients. However, when used in a high dose, it could cause a seizure in the postoperative period. The exact effector mechanism behind the seizure triggering remains unknown. Therefore, the authors investigated the effects of TXA on the activity of glutamate transporter type 3 (excitatory amino acid transporter 3; EAAT3), which is the main neuronal glutamate transporter type. Methods EAAT3 was expressed in Xenopus laevis oocytes through mRNA injection. Oocytes were incubated with diluted tranexamic acid for 72 h. Two-electrode voltage clamping was used to measure membrane currents before, during, and after applying 30 µM L-glutamate. Responses were quantified by integrating the current traces and reported in microcoulombs (µC). Results were presented as mean ± SEM. Results TXA (30 to 1,000 µM) significantly decreased EAAT3 activity. Our kinetic study showed that Vmax was significantly decreased in the TXA group compared with the control group (1.1 ± 0.1 vs. 1.4 ± 0.1 µC, n = 18–23, P = 0.043), but the Km did not significantly change (12.7 ± 3.9 µM for TXA vs. 12.8 ± 3.8 for control, n = 18–23, P = 0.986). Conclusions Our results suggest that TXA attenuates EAAT3 activity, which may explain its proconvulsant effect.http://www.anesth-pain-med.org/upload/pdf/apm-20004.pdfelectrophysiologyexcitatory amino acid transporter 3glutamate plasma membrane transport proteinstranexamic acidxenopus laevis |
| spellingShingle | Hyun-Jung Shin Soo-Young Lee Hyo-Seok Na Bon-Wook Koo Jung-Hee Ryu Sang-Hwan Do Effects of tranexamic acid on the activity of glutamate transporter EAAT3 Anesthesia and Pain Medicine electrophysiology excitatory amino acid transporter 3 glutamate plasma membrane transport proteins tranexamic acid xenopus laevis |
| title | Effects of tranexamic acid on the activity of glutamate transporter EAAT3 |
| title_full | Effects of tranexamic acid on the activity of glutamate transporter EAAT3 |
| title_fullStr | Effects of tranexamic acid on the activity of glutamate transporter EAAT3 |
| title_full_unstemmed | Effects of tranexamic acid on the activity of glutamate transporter EAAT3 |
| title_short | Effects of tranexamic acid on the activity of glutamate transporter EAAT3 |
| title_sort | effects of tranexamic acid on the activity of glutamate transporter eaat3 |
| topic | electrophysiology excitatory amino acid transporter 3 glutamate plasma membrane transport proteins tranexamic acid xenopus laevis |
| url | http://www.anesth-pain-med.org/upload/pdf/apm-20004.pdf |
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