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KMID : 1155520200150030291
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Anesthesia and Pain Medicine
2020 Volume.15 No. 3 p.291 ~ p.296
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Effects of tranexamic acid on the activity of glutamate transporter EAAT3
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Shin Hyun-Jung
Lee Soo-Young
Na Hyo-Seok
Koo Bon-Wook
Ryu Jung-Hee
Do Sang-Hwan
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Abstract
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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.
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KEYWORD
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Electrophysiology, Excitatory amino acid transporter 3, Glutamate plasma membrane transport proteins, Tranexamic acid, Xenopus laevis
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