TY - JOUR
T1 - Na+/Ca2+ exchanger maintains ionic homeostasis in the peri-infarct area
AU - Tortiglione, Anna
AU - Picconi, Barbara
AU - Barone, Ilaria
AU - Centonze, Diego
AU - Rossi, Silvia
AU - Costa, Cinzia
AU - Di Filippo, Massimiliano
AU - Tozzi, Alessandro
AU - Tantucci, Michela
AU - Bernardi, Giorgio
AU - Annunziato, Lucio
AU - Calabresi, Paolo
PY - 2007/5
Y1 - 2007/5
N2 - 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.
AB - 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.
KW - Electrophysiology
KW - Field potential
KW - Ischemia
KW - Na/Ca exchanger
KW - Permanent middle cerebral artery occlusion
KW - Striatum
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U2 - 10.1161/STROKEAHA.106.478644
DO - 10.1161/STROKEAHA.106.478644
M3 - Article
C2 - 17395860
AN - SCOPUS:34247599325
VL - 38
SP - 1614
EP - 1620
JO - Stroke
JF - Stroke
SN - 0039-2499
IS - 5
ER -