Deletion of the potassium channel Kv12.2 causes hippocampal hyperexcitability and epilepsy.
We found the voltage-gated K+ channel Kv12.2 to be a potent regulator of excitability in hippocampal pyramidal neurons. Genetic deletion and pharmacologic block of Kv12.2 substantially reduced the firing threshold of these neurons. Kv12.2-/- (also known as Kcnh3-/-) mice showed signs of persistent neuronal hyperexcitability including frequent interictal spiking, spontaneous seizures and increased sensitivity to the chemoconvulsant pentylenetetrazol.
Zhang
Xiaofei
X
Department of Cell Biology, The Scripps Research Institute, La Jolla, California, USA.
Bertaso
Federica
F
Yoo
Jong W
JW
Baumgärtel
Karsten
K
Clancy
Sinead M
SM
Lee
Van
V
Cienfuegos
Cynthia
C
Wilmot
Carly
C
Avis
Jacqueline
J
Hunyh
Truc
T
Daguia
Catherine
C
Schmedt
Christian
C
Noebels
Jeffrey
J
Jegla
Timothy
T
D000200:Action Potentials / Q000187:drug effects / Q000502:physiology; D000818:Animals; D002460:Cell Line; D002478:Cells, Cultured; D003292:Convulsants / Q000633:toxicity; D004827:Epilepsy / Q000139:chemically induced / Q000235:genetics / Q000503:physiopathology*; D051638:Ether-A-Go-Go Potassium Channels / Q000037:antagonists & inhibitors / Q000235:genetics / Q000378:metabolism*; D005260:Female; D006624:Hippocampus / Q000187:drug effects / Q000503:physiopathology*; D006801:Humans; D066298:In Vitro Techniques; D008297:Male; D008564:Membrane Potentials / Q000187:drug effects / Q000502:physiology; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D009474:Neurons / Q000187:drug effects / Q000502:physiology*; D010433:Pentylenetetrazole / Q000633:toxicity; D017966:Pyramidal Cells / Q000187:drug effects / Q000503:physiopathology; D012640:Seizures / Q000139:chemically induced / Q000235:genetics / Q000503:physiopathology; D014741:Video Recording; D014981:Xenopus
D003292:Convulsants; D051638:Ether-A-Go-Go Potassium Channels; C496887:Kcnh3 protein, mouse; D010433:Pentylenetetrazole