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Recent Advances in Epilepsy Research pp 76–91Cite as

Role of the GABA Transporter in Epilepsy

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Part of the book series: Advances in Experimental Medicine and Biology ((AEMB,volume 548))

Abstract

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.

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Authors
  1. George B. Richerson
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  2. Yuanming Wu
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Editors and Affiliations

  1. Department of Neurological Surgery, Moffitt Hospital, University of California at San Francisco, San Francisco, California, USA

    Devin K. Binder

  2. Center for Neural Recovery and Rehabilitation Research, New York State Department of Health, Helen Hayes Hospital, West Haverstraw, New York, USA

    Helen E. Scharfman

  3. Departments of Pharmacology and Neurology, Columbia University, New York, New York, USA

    Helen E. Scharfman

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Richerson, G.B., Wu, Y. (2004). Role of the GABA Transporter in Epilepsy. In: Binder, D.K., Scharfman, H.E. (eds) Recent Advances in Epilepsy Research. Advances in Experimental Medicine and Biology, vol 548. Springer, Boston, MA. https://doi.org/10.1007/978-1-4757-6376-8_6

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  • DOI: https://doi.org/10.1007/978-1-4757-6376-8_6

  • Publisher Name: Springer, Boston, MA

  • Print ISBN: 978-1-4419-3418-5

  • Online ISBN: 978-1-4757-6376-8

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