Amiloride suppresses pilocarpine-induced seizures via ASICs other than NHE in rats.

Background And Purpose: Although recent studies have indicated that acid-sensing ion channels (ASICs) may play an important role in suppressing status epilepticus (SE) in rats, the precise mechanism is unclear. We attempted to investigate the antiepileptic effect of amiloride in SE rats and its mechanism.

Methods: Rats with seizures induced by Li-pilocarpine were randomly divided into four groups, phosphate buffer saline (PBS) group, amiloride group, levetiracetam group and acidic liquid group, respectively. The electroencephalogram (EEG) of each group was recorded. Then rats treated with different drugs (2 h after amiloride or PBS injection or 1 h after PBS injection) and a normal control group was selected for reverse transcription-polymerase chain reaction (RT-PCR). The expression of ASIC1a, ASIC3 and sodium-hydrogen exchanger (NHE) in each group was detected.

Results: Amiloride reduced the frequency of discharge in 60~90 min after injection significantly. In acidic liquid group, the epileptic discharge was increased in 0~30 min. Moreover, the expression of ASIC1a, ASIC3 and NHE was obviously increased in the SE groups. Compared with SE groups, the expression of ASIC1a and ASIC3 mRNA in amiloride group decreased significantly. While NHE mRNA expression in the SE groups showed no significant difference.

Conclusion: Amiloride inhibited pilocarpine-induced SE and the anti-epileptic mechanism was associated with deactivation of the ASIC1a and ASIC3 instead of NHE in rats.