Inhibition of NKCC1 attenuated hippocampal LTP formation and inhibitory avoidance in rat

Meng Chang Ko, Min Chong Lee, Tamara G. Amstislavskay, Maria A. Tikhonova, Yi Ling Yang, Kwok Tung Lu

Research output: Contribution to journalArticle

3 Citations (Scopus)

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.

Original languageEnglish
Article numbere106692
JournalPloS one
Volume9
Issue number11
DOIs
Publication statusPublished - 2014 Nov 4

Fingerprint

Bumetanide
anticonvulsants
diuretics
hippocampus
Rats
Hippocampus
learning
rats
intravenous injection
Avoidance Learning
Sodium Potassium Chloride Symporter Inhibitors
phosphorylation
cations
chlorides
Western blotting
brain
Anticonvulsants
dosage
Phosphorylation
Long-Term Potentiation

ASJC Scopus subject areas

  • Biochemistry, Genetics and Molecular Biology(all)
  • Agricultural and Biological Sciences(all)
  • General

Cite this

Ko, M. C., Lee, M. C., Amstislavskay, T. G., Tikhonova, M. A., Yang, Y. L., & Lu, K. T. (2014). Inhibition of NKCC1 attenuated hippocampal LTP formation and inhibitory avoidance in rat. PloS one, 9(11), [e106692]. https://doi.org/10.1371/journal.pone.0106692

Inhibition of NKCC1 attenuated hippocampal LTP formation and inhibitory avoidance in rat. / Ko, Meng Chang; Lee, Min Chong; Amstislavskay, Tamara G.; Tikhonova, Maria A.; Yang, Yi Ling; Lu, Kwok Tung.

In: PloS one, Vol. 9, No. 11, e106692, 04.11.2014.

Research output: Contribution to journalArticle

Ko, Meng Chang ; Lee, Min Chong ; Amstislavskay, Tamara G. ; Tikhonova, Maria A. ; Yang, Yi Ling ; Lu, Kwok Tung. / Inhibition of NKCC1 attenuated hippocampal LTP formation and inhibitory avoidance in rat. In: PloS one. 2014 ; Vol. 9, No. 11.
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