In:
Stroke, Ovid Technologies (Wolters Kluwer Health), Vol. 38, No. 5 ( 2007-05), p. 1614-1620
Abstract:
Background and Purpose— A prominent feature of cerebral ischemia is the excessive intracellular accumulation of both Na + and Ca 2+ ions, which results in subsequent cell death. The plasma membrane Na + /Ca 2+ 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 (IC 50 =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) (IC 50 =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.
Type of Medium:
Online Resource
ISSN:
0039-2499
,
1524-4628
DOI:
10.1161/STROKEAHA.106.478644
Language:
English
Publisher:
Ovid Technologies (Wolters Kluwer Health)
Publication Date:
2007
detail.hit.zdb_id:
1467823-8
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