Role of the GABA Transporter in Epilepsy

  • George B. Richerson
  • Yuanming Wu
Part of the Advances in Experimental Medicine and Biology book series (AEMB, volume 548)


The GABA transporter plays a well-established role in reuptake of GABA after synaptic release. The anticonvulsant effect of tiagabine appears to result largely from blocking this reuptake. However, there is another side to the GABA transporter, contributing to GABA release by reversing in response to depolarization. We have recently shown that this form of GABA release is induced by even small increases in extracellular [K+], and has a powerful inhibitory effect on surrounding neurons. This transporter-mediated GABA release is enhanced by the anticonvulsants gabapentin and vigabatrin. The latter drug also potently increases ambient [GABA], inducing tonic inhibition of neurons. Here we review the evidence in support of a physiological role for GABA transporter reversal, and the evidence that it is increased by high-frequency firing. We postulate that the GABA transporter is a major determinant of the level of tonic inhibition, and an important source of GABA release during seizures. These recent findings indicate that the GABA transporter plays a much more dynamic role in control of brain excitability than has previously been recognized. Further defining this role may lead to a better understanding of the mechanisms of epilepsy and new avenues for treatment.


GABAA Receptor Gaba Release Tonic Inhibition Tetanus Toxin Gaba Transporter 
These keywords were added by machine and not by the authors. This process is experimental and the keywords may be updated as the learning algorithm improves.


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© Springer Science+Business Media New York 2004

Authors and Affiliations

  • George B. Richerson
  • Yuanming Wu

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