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GABA(A) receptor internalization during seizures.
Epilepsia. 2007; 48 Suppl 5:109-13.E

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.

Authors+Show Affiliations

Department of Neurology, University of Virginia, Health Sciences Center, Charlottesville, Virginia 22908, USA.No affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info available

Pub Type(s)

Journal Article
Research Support, N.I.H., Extramural

Language

eng

PubMed ID

17910589

Citation

Goodkin, Howard P., et al. "GABA(A) Receptor Internalization During Seizures." Epilepsia, vol. 48 Suppl 5, 2007, pp. 109-13.
Goodkin HP, Sun C, Yeh JL, et al. GABA(A) receptor internalization during seizures. Epilepsia. 2007;48 Suppl 5:109-13.
Goodkin, H. P., Sun, C., Yeh, J. L., Mangan, P. S., & Kapur, J. (2007). GABA(A) receptor internalization during seizures. Epilepsia, 48 Suppl 5, 109-13.
Goodkin HP, et al. GABA(A) Receptor Internalization During Seizures. Epilepsia. 2007;48 Suppl 5:109-13. PubMed PMID: 17910589.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - GABA(A) receptor internalization during seizures. AU - Goodkin,Howard P, AU - Sun,Chengsan, AU - Yeh,Jwu-Lai, AU - Mangan,Patrick S, AU - Kapur,Jaideep, PY - 2007/10/4/pubmed PY - 2007/11/14/medline PY - 2007/10/4/entrez SP - 109 EP - 13 JF - Epilepsia JO - Epilepsia VL - 48 Suppl 5 N2 - 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. SN - 0013-9580 UR - https://www.unboundmedicine.com/medline/citation/17910589/GABA_A__receptor_internalization_during_seizures_ L2 - https://doi.org/10.1111/j.1528-1167.2007.01297.x DB - PRIME DP - Unbound Medicine ER -