Relationship between neuronal vulnerability and potassium-chloride cotransporter 2 immunoreactivity in hippocampus following transient forebrain ischemia

E. Papp, C. Rivera, K. Kaila, T. Freund

Research output: Contribution to journalArticle

52 Citations (Scopus)

Abstract

Cation chloride cotransporters have been reported to be expressed in neurons in the hippocampus and to regulate intracellular Cl- concentration. The neuron-specific K-Cl cotransporter 2 (KCC2) is necessary for maintaining the low intracellular chloride concentration required for the hyperpolarizing actions of GABA. In this study we examined the vulnerability of KCC2-containing neurons as well as the changes in the pattern of KCC2 distribution in the rat hippocampus following 15 min ischemia induced by four-vessel occlusion. Immunostaining for the 72 kDa heat shock protein (HSP-72) was used to investigate the extent of damage in neuronal populations previously shown to be vulnerable to ischemia. At 6-24 h after ischemia, when the pyramidal cells in the CA1 (subfield of cornu Ammonis) region showed no morphological signs of damage, a small rise of KCC2 immunoreactivity was already observed. After 2 days, when the CA1 pyramidal cells started to degenerate, a progressive downregulation of the KCC2 protein was visible. Interestingly, in the same areas, the parvalbumin containing interneurons showed no signs of ischemic damage, and KCC2 immunoreactivity was retained on their membrane surface. In CA1 pyramidal cells, the reduction in KCC2 expression may lead to an elevation of intracellular Cl- concentration, which causes a shift in equilibrium potential toward more positive levels. Consequently, the reduction of the inhibitory action of GABA through downregulation of KCC2 function may be involved in the pathomechanisms of delayed neuronal death in the CA1 subfield.

Original languageEnglish
Pages (from-to)677-689
Number of pages13
JournalNeuroscience
Volume154
Issue number2
DOIs
Publication statusPublished - Jun 23 2008

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Prosencephalon
Hippocampus
Ischemia
Pyramidal Cells
Neurons
gamma-Aminobutyric Acid
Chlorides
Down-Regulation
HSP72 Heat-Shock Proteins
Parvalbumins
potassium-chloride symporters
Interneurons
Cations
Membranes
Population

Keywords

  • GABA
  • heat-shock protein-72
  • hippocampus
  • KCC2
  • transient forebrain ischemia

ASJC Scopus subject areas

  • Neuroscience(all)

Cite this

Relationship between neuronal vulnerability and potassium-chloride cotransporter 2 immunoreactivity in hippocampus following transient forebrain ischemia. / Papp, E.; Rivera, C.; Kaila, K.; Freund, T.

In: Neuroscience, Vol. 154, No. 2, 23.06.2008, p. 677-689.

Research output: Contribution to journalArticle

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