Selective changes in single cell GABA(A) receptor subunit expression and function in temporal lobe epilepsy.
Temporal lobe epilepsy is the most prevalent seizure disorder in adults. Compromised inhibitory neurotransmitter function in the hippocampus contributes to the hyperexcitability generating this condition, but the underlying molecular mechanisms are unknown. Combining patch-clamp recording and single-cell mRNA amplification (aRNA) techniques in single dentate granule cells, we demonstrate that expression of GABA(A) receptor subunit mRNAs is substantially altered in neurons from epileptic rats. These changes in gene expression precede epilepsy onset by weeks and correlate with profound alterations in receptor function, indicating that aberrant GABA(A) receptor expression and function has an essential role in the process of epileptogenesis.
Joseph Stokes Research Institute of The Children's Hospital of Philadelphia, Department of Neurology, University of Pennsylvania, 19104, USA. kayal@email.chop.edu
A R
AR
Brooks-Kayal
M D
MD
Shumate
H
H
Jin
T Y
TY
Rikhter
D A
DA
Coulter
D000818:Animals; D002469:Cell Separation; D018891:Dentate Gyrus / Q000166:cytology / Q000378:metabolism*; D004553:Electric Conductivity; D004833:Epilepsy, Temporal Lobe / Q000139:chemically induced / Q000378:metabolism*; D005786:Gene Expression Regulation; D006651:Histocytochemistry; D009474:Neurons / Q000166:cytology / Q000378:metabolism; D018408:Patch-Clamp Techniques; D010862:Pilocarpine / Q000494:pharmacology; D012333:RNA, Messenger / Q000032:analysis; D051381:Rats; D011963:Receptors, GABA-A / Q000096:biosynthesis* / Q000235:genetics; D012640:Seizures / Q000139:chemically induced
D012333:RNA, Messenger; D011963:Receptors, GABA-A; D010862:Pilocarpine