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.
- Field potential
- Na/Ca exchanger
- Permanent middle cerebral artery occlusion
ASJC Scopus subject areas
- Cardiology and Cardiovascular Medicine