Na+-K+-Cl- cotransporter isoform 1 (NKCC1) and Na+/Ca2+ exchanger isoform 1 (NCX1) were expressed in cortical neurons. Three hours of oxygen and glucose deprivation (OGD) significantly increased expression of full-length NCX1 protein (∼116 kDa), which remained elevated during 1 to 21 h reoxygenation (REOX) and was accompanied with concurrent cleavage of NCX1. Na+/Ca2+ exchanger isoform 1 heterozygous (NCX1+/-) neurons with ∼50% less of NCX1 protein exhibited ∼64% reduction in NCX-mediated Ca2+ influx. Expression of NCX1 and NKCC1 proteins was reduced in double heterozygous (NCX1+/-/NKCC1+/-) neurons. NCX-mediated Ca2+ influx was nearly abolished in these neurons. Three-hour OGD and 21-h REOX caused ∼80% mortality rate in NCX1+/+ neurons and in NCX1 +/- neurons. In contrast, NKCC1+/- neurons exhibited ∼45% less cell death. The lowest mortality rate was found in NCX1 +/-/NKCC1+/- neurons (∼65% less neuronal death). The increased tolerance to ischemic damage was also observed in NCX1 +/-/NKCC1+/- brains after transient cerebral ischemia. NCX1+/-/NKCC1+/- mice had a significantly reduced infarct volume at 24 and 72 h reperfusion. In conclusion, these data suggest that NKCC1 in conjunction with NCX1 plays a role in reperfusion-induced brain injury after ischemia.
|Original language||English (US)|
|Number of pages||10|
|Journal||Journal of Cerebral Blood Flow and Metabolism|
|State||Published - Apr 2008|
- Ca overload
- Focal ischemia
- Neuronal death