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Related Experiment Video

Updated: May 7, 2026

Electroconvulsive Seizures in Rats and Fractionation of Their Hippocampi to Examine Seizure-induced Changes in Postsynaptic Density Proteins

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Published on: August 15, 2017

NKCC1 transporter facilitates seizures in the developing brain.

Volodymyr I Dzhala¹, Delia M Talos, Dan A Sdrulla

¹Department of Neurology, School of Medicine, University of Colorado Health Sciences Center, 4200 East Ninth Avenue, Denver, Colorado 80262, USA.

Nature Medicine

|October 18, 2005

Summary

The Na(+)-K(+)-2Cl(-) cotransporter (NKCC1) facilitates neonatal seizures by increasing intracellular chloride. Blocking NKCC1 with bumetanide effectively treats seizures in developing brains, offering a potential therapeutic strategy.

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Published on: December 9, 2022

Area of Science:

Neuroscience
Developmental Biology
Pharmacology

Background:

Neuronal excitation by GABA(A) receptors (GABA(A)-R) during development is due to high intracellular chloride (Cl(-)) levels.
GABAergic inhibition develops with outward Cl(-) transport, progressing from caudal to rostral brain regions.
This developmental pattern explains why GABAergic drugs treat neonatal motor seizures but not cortical seizures.

Purpose of the Study:

To investigate the role of the Na(+)-K(+)-2Cl(-) cotransporter (NKCC1) in neonatal seizures.
To evaluate the efficacy of the NKCC1 blocker bumetanide as a treatment for neonatal seizures.

Main Methods:

Examined the effect of bumetanide on chloride equilibrium potential (E(Cl)) in immature neurons.
Assessed bumetanide's impact on epileptiform activity in rat hippocampal slices and electrographic seizures in neonatal rats.
Compared NKCC1 and KCC2 expression levels in human and rat cortex during development.

Main Results:

Bumetanide shifted E(Cl) to more negative values in immature neurons.
Bumetanide suppressed in vitro epileptiform activity and in vivo electrographic seizures in neonatal rats.
NKCC1 expression was high relative to KCC2 in perinatal human and rat cortex, indicating immature Cl(-) transport.

Conclusions:

NKCC1 actively facilitates seizures in the developing brain.
Bumetanide demonstrates significant potential for treating neonatal seizures by targeting NKCC1-mediated Cl(-) accumulation.