GABAA Receptor Internalization during Seizures

Authors


Address correspondence and reprint requests to Jaideep Kapur, MD, Ph.D, Department of Neurology, Box 800394, University of Virginia-HSC, Charlottesville, VA 22908. E-mail: jk8t@virginia.edu

Abstract

Summary:  A rapid modification in the postsynaptic γ-aminobutyric acid (GABAA) 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 GABAA receptor subunits and that the constitutive internalization of GABAA receptors containing a β2/3 subunit was rapid and activity-dependent. Based on this finding, we posit that an activity-dependent increase in the rate of internalization of synaptic GABAA receptors during SE contributes to the reduction in inhibitory transmission and the development of benzodiazepine pharmacoresistance.

Ancillary