Ontogeny of cation–Cl− cotransporter expression in rat neocortex

Clayton, Gerald H.; Owens, Geoffrey C.; Wolff, Jason S; Smith, Roderic L.

doi:10.1016/s0165-3806(98)00078-9

Cited by 208 publications

(165 citation statements)

References 49 publications

Supporting

Mentioning

153

Contrasting

Unclassified

Order By: Relevance

“…2 A, B), which was not further evaluated. The low or absent neuronal expression of NKCC1 in controls is in line with previous studies in adult rats (Clayton et al, 1998;Marty et al, 2002;Bragin et al, 2009). Twenty-four hours after SE, intense neuronal staining was observed in the subiculum, CA1, CA3, and dentate granule cell layer.…”

Section: Alterations In Nkcc1 Immunoreactivity After Sesupporting

confidence: 91%

Disease-Modifying Effects of Phenobarbital and the NKCC1 Inhibitor Bumetanide in the Pilocarpine Model of Temporal Lobe Epilepsy

Brandt¹,

Nozadze²,

Heuchert³

et al. 2010

Journal of Neuroscience

164

166

View full text Add to dashboard Cite

Accumulating evidence suggests that changes in neuronal chloride homeostasis may be involved in the mechanisms by which brain insults induce the development of epilepsy. A variety of brain insults, including status epilepticus (SE), lead to changes in the expression of the cation-chloride cotransporters KCC2 and NKCC1, resulting in intracellular chloride accumulation and reappearance of immature, depolarizing synaptic responses to GABA A receptor activation, which may critically contribute to the neuronal hyperexcitability underlying epileptogenesis. In the present study, it was evaluated whether prolonged administration of the selective NKCC1 inhibitor, bumetanide, after a pilocarpine-induced SE modifies the development of epilepsy in adult female rats. The antiepileptic drug phenobarbital, either alone or in combination, was used for comparison. Based on pharmacokinetic studies with bumetanide, which showed extremely rapid elimination and low brain penetration of this drug in rats, bumetanide was administered systemically with different dosing protocols, including continuous intravenous infusion. As shown by immunohistochemistry, neuronal NKCC1 expression was markedly upregulated shortly after SE. Prophylactic treatment with phenobarbital after SE reduced the number of rats developing spontaneous seizures and decreased seizure frequency, indicating a disease-modifying effect. Bumetanide did not exert any significant effects on development of spontaneous seizures nor did it enhance the effects of phenobarbital. However, combined treatment with both drugs counteracted several of the behavioral consequences of SE, which was not observed with single drug treatment. These data do not indicate that bumetanide can prevent epilepsy after SE, but the disease-modifying effect of this drug warrants further studies with more lipophilic prodrugs of bumetanide.

show abstract

Section: Alterations In Nkcc1 Immunoreactivity After Sesupporting

confidence: 91%

Disease-Modifying Effects of Phenobarbital and the NKCC1 Inhibitor Bumetanide in the Pilocarpine Model of Temporal Lobe Epilepsy

Brandt¹,

Nozadze²,

Heuchert³

et al. 2010

Journal of Neuroscience

164

166

View full text Add to dashboard Cite

show abstract

“…The Na-K-2Cl cotransporter NKCC1, which uses the inwardly directed sodium gradient to raise [Cl Ϫ ] i , shows a decreasing neuronal expression during postnatal development (Clayton et al, 1998;Hübner et al, 2001a). Inhibition of Na-K-2Cl cotransport by bumetanide causes a hyperpolarizing shift of the GABA reversal potential in rat neocortical neurons (Yamada et al, 2004) and in hippocampal neurons (Dzhala et al, 2005;Sipilä et al, 2006).…”

Section: Introductionmentioning

confidence: 99%

NKCC1-Dependent GABAergic Excitation Drives Synaptic Network Maturation during Early Hippocampal Development

Pfeffer¹,

Stein²,

Keating³

et al. 2009

J. Neurosci.

131

129

View full text Add to dashboard Cite

A high intracellular chloride concentration in immature neurons leads to a depolarizing action of GABA that is thought to shape the developing neuronal network. We show that GABA-triggered depolarization and Ca 2ϩ transients were attenuated in mice deficient for the Na-K-2Cl cotransporter NKCC1. Correlated Ca 2ϩ transients and giant depolarizing potentials (GDPs) were drastically reduced and the maturation of the glutamatergic and GABAergic transmission in CA1 delayed. Brain morphology, synaptic density, and expression levels of certain developmental marker genes were unchanged. The expression of lynx1, a protein known to dampen network activity, was decreased. In mice deficient for the neuronal Cl Ϫ /HCO 3 Ϫ exchanger AE3, GDPs were also diminished. These data show that NKCC1-mediated Cl Ϫ accumulation contributes to GABAergic excitation and network activity during early postnatal development and thus facilitates the maturation of excitatory and inhibitory synapses.

show abstract

“…Na ϩ -K ϩ -2Cl Ϫ cotransporters (NKCC) (in the brain found in its isoform NKCC1) mediate active Cl Ϫ uptake and are thus appropriate candidates for neuronal Cl Ϫ accumulation (Delpire, 2000;Payne et al, 2003). Expression levels of NKCC1 have been reported to be high at birth and to decline subsequently (Plotkin et al, 1997;Yamada et al, 2004), whereas other studies reported NKCC1 upregulation or redistribution during early development of CNS (Clayton et al, 1998;Marty et al, 2002). Several studies found that Na ϩ -depleted solutions and loop diuretics, which both reduce the activity of NKCC1 (Russell, 2000), decrease steady-state [Cl Ϫ ] i in immature neurons, suggesting a role for NKCC1 in the maintenance of high [Cl Ϫ ] i (Rohrbough and Spitzer, 1996;Kakazu et al, 1999;Ikeda et al, 2003;Yamada et al, 2004).…”

Section: Introductionmentioning

confidence: 99%

Kinetic Properties of Cl⁻Uptake Mediated by Na⁺-Dependent K⁺-2Cl⁻Cotransport in Immature Rat Neocortical Neurons

Achilles¹,

Okabe²,

Ikeda³

et al. 2007

J. Neurosci.

155

170

View full text Add to dashboard Cite

show abstract

Ontogeny of cation–Cl− cotransporter expression in rat neocortex

Cited by 208 publications

References 49 publications

Disease-Modifying Effects of Phenobarbital and the NKCC1 Inhibitor Bumetanide in the Pilocarpine Model of Temporal Lobe Epilepsy

Disease-Modifying Effects of Phenobarbital and the NKCC1 Inhibitor Bumetanide in the Pilocarpine Model of Temporal Lobe Epilepsy

NKCC1-Dependent GABAergic Excitation Drives Synaptic Network Maturation during Early Hippocampal Development

Kinetic Properties of Cl⁻Uptake Mediated by Na⁺-Dependent K⁺-2Cl⁻Cotransport in Immature Rat Neocortical Neurons

Contact Info

Product

Resources

About

Ontogeny of cation–Cl− cotransporter expression in rat neocortex

Cited by 208 publications

References 49 publications

Disease-Modifying Effects of Phenobarbital and the NKCC1 Inhibitor Bumetanide in the Pilocarpine Model of Temporal Lobe Epilepsy

Disease-Modifying Effects of Phenobarbital and the NKCC1 Inhibitor Bumetanide in the Pilocarpine Model of Temporal Lobe Epilepsy

NKCC1-Dependent GABAergic Excitation Drives Synaptic Network Maturation during Early Hippocampal Development

Kinetic Properties of Cl−Uptake Mediated by Na+-Dependent K+-2Cl−Cotransport in Immature Rat Neocortical Neurons

Contact Info

Product

Resources

About

Kinetic Properties of Cl⁻Uptake Mediated by Na⁺-Dependent K⁺-2Cl⁻Cotransport in Immature Rat Neocortical Neurons