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GABA A Receptor Internalization during Seizures
Author(s) -
Goodkin Howard P.,
Sun Chengsan,
Yeh JwuLai,
Mangan Patrick S.,
Kapur Jaideep
Publication year - 2007
Publication title -
epilepsia
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.687
H-Index - 191
eISSN - 1528-1167
pISSN - 0013-9580
DOI - 10.1111/j.1528-1167.2007.01297.x
Subject(s) - internalization , gabaa receptor , receptor , neuroscience , inhibitory postsynaptic potential , postsynaptic potential , population , biology , neurotransmission , chemistry , microbiology and biotechnology , biochemistry , medicine , environmental health
Summary: A rapid modification in the postsynaptic γ‐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 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 GABA A receptors during SE contributes to the reduction in inhibitory transmission and the development of benzodiazepine pharmacoresistance.