Overexpression of gamma-aminobutyric acid transporter subtype I leads to susceptibility to kainic acid-induced seizure in transgenic mice.
Gamma-aminobutyric acid (GABA) is the principal inhibitory neurotransmitter, and the GABAergic synaptic transmission is normally terminated by the rapid uptake through GABA transporters. With transgenic mice ubiquitously overexpressing GABA transporter subtype I (GAT1), the present study explored the pathophysiological role of GAT1 in epileptogenesis. Though displaying no spontaneous seizure activity, these mice exhibit altered electroencephalographic patterns and increased susceptibility to seizure induced by kainic acid. In addition, the GABA(A) receptor and glutamate transporters are up-regulated in transgenic mice, which perhaps reflects a compensatory or corrective change to the elevated level of GAT1. These preliminary findings support the hypothesis that excitatory and inhibitory neurotransmission, and seizure susceptibility can be altered by neurotransmitter transporters.
Ma
Y
Y
Institute of Biochemistry and Cell Biology, Shanghai Institutes for Biological Sciences, Chinese Academy of Sciences.
Hu
J H
JH
Zhao
W J
WJ
Fei
J
J
Yu
Y
Y
Zhou
X G
XG
Mei
Z T
ZT
Guo
L H
LH
D018528:ATP-Binding Cassette Transporters / Q000235:genetics / Q000378:metabolism; D000200:Action Potentials / Q000235:genetics; D027322:Amino Acid Transport System X-AG; D000818:Animals; D001921:Brain / Q000378:metabolism* / Q000503:physiopathology; D002352:Carrier Proteins / Q000235:genetics* / Q000378:metabolism; D004569:Electroencephalography; D018690:Excitatory Amino Acid Agonists / Q000494:pharmacology; D050485:GABA Plasma Membrane Transport Proteins; D005786:Gene Expression Regulation / Q000235:genetics; D020022:Genetic Predisposition to Disease / Q000235:genetics*; D018698:Glutamic Acid / Q000378:metabolism / Q000493:pharmacokinetics; D007608:Kainic Acid / Q000494:pharmacology; D008565:Membrane Proteins / Q000235:genetics* / Q000378:metabolism; D026901:Membrane Transport Proteins; D051379:Mice; D008822:Mice, Transgenic; D009433:Neural Inhibition / Q000235:genetics*; D009474:Neurons / Q000378:metabolism*; D027361:Organic Anion Transporters; D011963:Receptors, GABA-A / Q000235:genetics / Q000378:metabolism; D012640:Seizures / Q000139:chemically induced / Q000235:genetics* / Q000503:physiopathology; D013574:Synaptosomes / Q000187:drug effects / Q000378:metabolism; D015854:Up-Regulation / Q000235:genetics; D005680:gamma-Aminobutyric Acid / Q000378:metabolism* / Q000493:pharmacokinetics
D018528:ATP-Binding Cassette Transporters; D027322:Amino Acid Transport System X-AG; D002352:Carrier Proteins; D018690:Excitatory Amino Acid Agonists; D050485:GABA Plasma Membrane Transport Proteins; D008565:Membrane Proteins; D026901:Membrane Transport Proteins; D027361:Organic Anion Transporters; D011963:Receptors, GABA-A; C493414:Slc6a1 protein, mouse; D018698:Glutamic Acid; D005680:gamma-Aminobutyric Acid; D007608:Kainic Acid