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Epilepsia. 2007;48 Suppl 5:109-13.

GABA(A) receptor internalization during seizures.

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1
Department of Neurology, University of Virginia, Health Sciences Center, Charlottesville, Virginia 22908, USA.

Erratum in

  • Epilepsia. 2007 Dec;48(12):2380.

Abstract

A rapid modification in the postsynaptic gamma-aminobutyric acid (GABA(A)) receptor population occurs during the prolonged seizures of status epilepticus (SE). This rapid modification contributes to a reduction in GABA-mediated inhibition and the development of benzodiazepine pharmacoresistance. Previous hypotheses to explain the modification have included an alteration in the structural composition or posttranslational modification of the receptors. In a cultured hippocampal neuron model, we found that there was differential subcellular distribution of GABA(A) receptor subunits and that the constitutive internalization of GABA(A) receptors containing a beta2/3 subunit was rapid and activity-dependent. Based on this finding, we posit that an activity-dependent increase in the rate of internalization of synaptic GABA(A) receptors during SE contributes to the reduction in inhibitory transmission and the development of benzodiazepine pharmacoresistance.

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