Up-regulated astroglial TWIK-related acid-sensitive K+ channel-1 (TASK-1) in the hippocampus of seizure-sensitive gerbils: a target of anti-epileptic drugs.
In order to identify the modulation of TASK (TWIK-related Acid-Sensitive K(+)) channel expressions in epilepsy, we conducted a comparative analysis of TASK channel immunoreactivities in the hippocampus of seizure-resistant (SR) and seizure-sensitive (SS) gerbils. There was no difference of the TASK-1 and TASK-2 channel expressions in the hippocampi of young SR and SS gerbils (1-2 months old). In adult SS gerbil hippocampus, TASK-1 immunoreactivity in astrocytes was higher than that in adult SR gerbil hippocampus. After seizures, TASK-1 immunoreactivity was significantly down-regulated in astrocytes of the SS gerbil hippocampus. In addition, various anti-epileptic drugs selectively affect TASK-1 immunoreactivity in astrocytes of the SS gerbil hippocampus. Gabapentin, lamotrigine, topiramate and valproic acid reduced the number of TASK-1(+) astrocytes in the hippocampus to 10-25% of that in saline-treated SS adult gerbils, whereas carbamazepine and vigabatrin decreased to approximately 50%. Therefore, the present study demonstrates that up-regulated TASK-1 immunoreactivity in astrocytes may be involved in the seizure activity of SS adult gerbils and suggests that the astroglial TASK-1 channel may be a target for epilepsy therapeutics.
Kim
Duk-Soo
DS
Department of Anatomy, College of Medicine, Hallym University, Chunchon 200-702, South Korea.
Kim
Ji-Eun
JE
Kwak
Sung-Eun
SE
Choi
Hui-Chul
HC
Song
Hong-Ki
HK
Kimg
Yeong-In
YI
Choi
Soo-Young
SY
Kang
Tae-Cheon
TC
D000367:Age Factors; D000704:Analysis of Variance; D000818:Animals; D000927:Anticonvulsants / Q000494:pharmacology; D001253:Astrocytes / Q000187:drug effects / Q000378:metabolism*; D001522:Behavior, Animal / Q000187:drug effects / Q000502:physiology; D002452:Cell Count / Q000379:methods; D004195:Disease Models, Animal; D005849:Gerbillinae; D005904:Glial Fibrillary Acidic Protein / Q000378:metabolism; D006624:Hippocampus / Q000378:metabolism / Q000473:pathology*; D009419:Nerve Tissue Proteins / Q000235:genetics / Q000378:metabolism*; D024683:Potassium Channels, Tandem Pore Domain / Q000235:genetics / Q000378:metabolism*; D012640:Seizures / Q000188:drug therapy / Q000473:pathology* / Q000503:physiopathology*; D015854:Up-Regulation / Q000187:drug effects / Q000502:physiology*
D000927:Anticonvulsants; D005904:Glial Fibrillary Acidic Protein; D009419:Nerve Tissue Proteins; D024683:Potassium Channels, Tandem Pore Domain; C420132:potassium channel subfamily K member 3