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

Abstract

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.