Background: Clonidine has been shown to be a potent neuroprotectant by acting at α2 receptors on glutamatergicneurons to inhibit the release of glutamate. The aim of this study is to investigate the effects of clonidine on theactivity of EAAT3 that can regulate extracellular glutamate.Methods: EAAT3 was expressed in the Xenopus oocytes. Using a two-electrode voltage clamp, membrane currentswere recorded after application of 30 μM L-glutamate both in the presence and absence of various concentrationsof clonidine. To determine the effects of clonidine on the Km and Vmax of EAAT3 and the reversibility of clonidineeffects, membrane currents were recorded after the application of various concentrations of L-glutamate both in thepresence and absence of 1.50 × 10-7 M clonidine. Results: Clonidine reduced the EAAT3 responses to L-glutamate in a concentration-dependent manner. Thisinhibition was statistically significant at higher concentrations than at the clinically relevant range. Clonidine at 1.50× 10-7 M reduced the Vmax, but did not affect the Km of EAAT3 for L-glutamate.Conclusions: These results suggest that the direct inhibition of EAAT3 activity is not related to the sedation effectof clonidine and that the clonidine-induced reduction of EAAT3 activity provides additional data for the possibleinvolvement of glutamatergic hyperactivity in the proconvulsant effect of clonidine.
- Glutamate transporters