Na+/Ca2+ exchanger maintains ionic homeostasis in the peri-infarct area

Anna Tortiglione, Barbara Picconi, Ilaria Barone, Diego Centonze, Silvia Rossi, Cinzia Costa, Massimiliano Di Filippo, Alessandro Tozzi, Michela Tantucci, Giorgio Bernardi, Lucio Annunziato, Paolo Calabresi

Research output: Contribution to journalArticlepeer-review

Abstract

BACKGROUND AND PURPOSE - A prominent feature of cerebral ischemia is the excessive intracellular accumulation of both Na and Ca ions, which results in subsequent cell death. The plasma membrane Na/Ca exchanger (NCX), regulates the distribution of these ions acting either in the forward mode or in its reverse mode and it can play a critical role in brain ischemia. However, it is unclear whether the activity of NCX leads to detrimental or beneficial effects. METHODS - Extracellular field potentials and whole-cell patch clamp recordings were obtained from rat corticostriatal brain-slice preparations in the peri-infarct area 24 hours after the permanent middle cerebral artery occlusion. Ischemia was induced in rats by permanents middle cerebral artery occlusion. RESULTS - Bepridil, an inhibitor of NCX, reduced in a concentration-dependent manner (IC50=68 μmol/L) the field potential amplitude recorded from the peri-infarct area of corticostriatal slices. Conversely, no change was observed in sham-operated animals. The effect of bepridil was mimicked by 5-(N-4-chlorobenzyl)-2′,4′-dimethylbenzamil (CB-DMB) (IC50=6 μmol/L), a more selective inhibitor of NCX. In whole-cell patch clamp experiments, bepridil and CB-DMB caused an inward current in spiny neurons recorded from the peri-infarct area but not in the same cells recorded from controls. Interestingly, cholinergic interneurons recorded from the striatal peri-infarct area did not develop an inward current after the application of NCX inhibitors, suggesting that the electrophysiological alterations induced by NCX inhibition are cell-type specific. Bepridil and CB-DMB also induced a suppression of excitatory synaptic currents in most of spiny neurons recorded from the peri-infarct area. This effect was not coupled to a significant change of paired-pulse facilitation suggesting a postsynaptic site of action. CONCLUSIONS - Our data indicate that NCX plays a critical role in the maintenance of ionic homeostasis in the peri-infarct area.

Original languageEnglish
Pages (from-to)1614-1620
Number of pages7
JournalStroke
Volume38
Issue number5
DOIs
Publication statusPublished - May 2007

Keywords

  • Electrophysiology
  • Field potential
  • Ischemia
  • Na/Ca exchanger
  • Permanent middle cerebral artery occlusion
  • Striatum

ASJC Scopus subject areas

  • Cardiology and Cardiovascular Medicine
  • Neuroscience(all)

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