title: Inhibition of NKCC1 attenuated hippocampal LTP formation and inhibitory avoidance in rat.
abstract: The loop diuretic bumetanide (Bumex) is thought to have antiepileptic properties via modulate GABAA mediated signaling through their antagonism of cation-chloride cotransporters. Given that loop diuretics may act as antiepileptic drugs that modulate GABAergic signaling, we sought to investigate whether they also affect hippocampal function. The current study was performed to evaluate the possible role of NKCC1 on the hippocampal function. Brain slice extracellular recording, inhibitory avoidance, and western blot were applied in this study. Results showed that hippocampal Long-term potentiation was attenuated by suprafusion of NKCC1 inhibitor bumetanide, in a dose dependent manner. Sequent experiment result showed that Intravenous injection of bumetanide (15.2 mg/kg) 30 min prior to the training session blocked inhibitory avoidance learning significantly. Subsequent control experiment's results excluded the possible non-specific effect of bumetanide on avoidance learning. We also found the phosphorylation of hippocampal MAPK was attenuated after bumetanide administration. These results suggested that hippocampal NKCC1 may via MAPK signaling cascade to possess its function.
authors.affiliation: Department of Life Science, National Taiwan Normal University, Taipei, Taiwan.
authors.forename: Meng Chang
authors.initials: MC
authors.lastname: Ko
authors.affiliation: Department of Life Science, National Taiwan Normal University, Taipei, Taiwan.
authors.forename: Min Chong
authors.initials: MC
authors.lastname: Lee
authors.affiliation: Laboratory of Biological Psychiatry, State Research Institute of Physiology and Fundamental Medicine SB RAMS, Novosibirsk, Russia.
authors.forename: Tamara G
authors.initials: TG
authors.lastname: Amstislavskaya
authors.affiliation: Laboratory of Biological Psychiatry, State Research Institute of Physiology and Fundamental Medicine SB RAMS, Novosibirsk, Russia.
authors.forename: Maria A
authors.initials: MA
authors.lastname: Tikhonova
authors.affiliation: Department of Biochemical Science and Technology, National Chia-Yi University, Chia-Yi, Taiwan.
authors.forename: Yi-Ling
authors.initials: YL
authors.lastname: Yang
authors.affiliation: Department of Life Science, National Taiwan Normal University, Taipei, Taiwan.
authors.forename: Kwok-Tung
authors.initials: KT
authors.lastname: Lu
mesh_terms: D000818:Animals; D000927:Anticonvulsants / Q000494:pharmacology*; D001362:Avoidance Learning / Q000187:drug effects*; D002034:Bumetanide / Q000494:pharmacology; D006624:Hippocampus / Q000187:drug effects* / Q000378:metabolism; D017774:Long-Term Potentiation / Q000187:drug effects*; D008297:Male; D057567:Memory, Long-Term / Q000187:drug effects; D020928:Mitogen-Activated Protein Kinases / Q000378:metabolism; D009043:Motor Activity / Q000187:drug effects; D010766:Phosphorylation / Q000187:drug effects; D010852:Picrotoxin / Q000494:pharmacology; D051381:Rats; D017208:Rats, Wistar; D011963:Receptors, GABA-A / Q000378:metabolism; D015398:Signal Transduction / Q000187:drug effects; D064506:Solute Carrier Family 12, Member 2 / Q000737:chemistry / Q000378:metabolism*
chemical_list: D000927:Anticonvulsants; D002034:Bumetanide; D020928:Mitogen-Activated Protein Kinases; D010852:Picrotoxin; D011963:Receptors, GABA-A; D064506:Solute Carrier Family 12, Member 2