Effects of tranexamic acid on the activity of glutamate transporter EAAT3

Abstract

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 M L-glutamate. Responses were quantified by integrating the current traces and reported in microcoulombs (C). Results were presented as mean  SEM.Results: TXA (30 to 1,000 M) 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 C, n = 18–23, P = 0.043), but the Km did not significantly change (12.7  3.9 M 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.

The potential therapeutic roles of Rho GTPases in substance dependence

“…Similar to DAT, which is responsible for maintaining the DA concentration in the synaptic cleft, excitatory amino acid transporters (EAATs) are responsible for regulating the concentration of extracellular glutamate, which determines the spatial and temporal precision of glutamate neurotransmission and limits the excitotoxic effects of glutamate. EAAT3 is found predominantly in neurons and is the main subtype of glutamate transporter in dopaminergic neurons ( Shin et al, 2020 ). Amphetamine stimulated the internalization of EAAT3, which was dependent on the activation of a RhoA, dynamin, and the expression of DAT, and decreased glutamate uptake in cultured neurons ( Underhill et al, 2014 ).…”