Expression of functional Kir6.1 channels regulates glutamate release at CA3 synapses in generation of epileptic form of seizures.
The Kir6.1 channels are a subtype of ATP-sensitive inwardly rectifying potassium (K(ATP)) channels that play an essential role in coupling the cell's metabolic events to electrical activity. In this study, we show that functional Kir6.1 channels are located at excitatory pre-synaptic terminals as a complex with type-1 Sulfonylurea receptors (SUR1) in the hippocampus. The mutant mice with deficiencies in expressing the Kir6.1 or the SUR1 gene are more vulnerable to generation of epileptic form of seizures, compared to wild-type controls. Whole-cell patch clamp recordings demonstrate that genetic deletion of the Kir6.1/SUR1 channels enhances glutamate release at CA3 synapses. Hence, expression of functional Kir6.1/SUR1 channels inhibits seizure responses and possibly acts via limiting excitatory glutamate release.
Soundarapandian
Mangala M
MM
Biomedical Science Center, Burnett College of Biomedical Sciences, University of Central Florida, Orlando, Florida, USA.
Wu
Di
D
Zhong
Xiaofen
X
Petralia
Ronald S
RS
Peng
Lisheng
L
Tu
Weihong
W
Lu
Youming
Y
D000818:Animals; D001522:Behavior, Animal; D018690:Excitatory Amino Acid Agonists / Q000494:pharmacology; D005786:Gene Expression Regulation / Q000502:physiology*; D018698:Glutamic Acid / Q000378:metabolism*; D006624:Hippocampus / Q000166:cytology* / Q000378:metabolism; D006801:Humans; D047468:Immunoprecipitation / Q000379:methods; D066298:In Vitro Techniques; D054086:KATP Channels; D007608:Kainic Acid / Q000494:pharmacology; D008297:Male; D008564:Membrane Potentials / Q000187:drug effects / Q000528:radiation effects; D051379:Mice; D018345:Mice, Knockout; D018408:Patch-Clamp Techniques / Q000379:methods; D024661:Potassium Channels, Inwardly Rectifying / Q000172:deficiency / Q000502:physiology*; D051381:Rats; D017207:Rats, Sprague-Dawley; D012640:Seizures / Q000209:etiology* / Q000235:genetics / Q000503:physiopathology; D013569:Synapses / Q000187:drug effects / Q000378:metabolism*
D018690:Excitatory Amino Acid Agonists; D054086:KATP Channels; D024661:Potassium Channels, Inwardly Rectifying; C092520:uK-ATP-1 potassium channel; D018698:Glutamic Acid; D007608:Kainic Acid