Na(+)/Ca(2+) exchanger 2 is neuroprotective by exporting Ca(2+) during a transient focal cerebral ischemia in the mouse.
Na(+)/Ca(2+) exchanger (NCX), by mediating Na(+) and Ca(2+) fluxes bi-directionally, assumes a role in controlling the Ca(2+) homeostasis in the ischemic brain. It has been suggested that the three isoforms of NCX (NCX1, 2 and 3) may be differentially involved in permanent cerebral ischemia. However, the role of NCX2 has not been defined in ischemic reperfusion injury after a transient focal cerebral ischemia. Furthermore, it is not known whether NCX2 imports or exports intracellular Ca(2+) ([Ca(2+)](i)) following ischemia and reperfusion. To define the role of NCX2 in ischemia and reperfusion, we examined mice lacking NCX2, in vivo and in vitro. After an in vitro ischemia, a significantly slower recovery in population spike amplitudes, a sustained elevation of [Ca(2+)](i) and an increased membrane depolarization were developed in the NCX2-deficient hippocampus. Moreover, a transient focal cerebral ischemia in vivo produced a larger infarction and more cell death in the NCX2-deficient mouse brain. In particular, in the wild type brain, NCX2-expressing neurons were largely spared from cell death after ischemia. Our results suggest that NCX2 exports Ca(2+) in ischemia and thus protects neuronal cells from death by reducing [Ca(2+)](i) in the adult mouse brain.
Jeon
Daejong
D
Center for Neural Science, Korea Institute of Science and Technology, Seoul, Republic of Korea.
Chu
Kon
K
Jung
Keun-Hwa
KH
Kim
Manho
M
Yoon
Byung-Woo
BW
Lee
C Justin
CJ
Oh
Uhtaek
U
Shin
Hee-Sup
HS
D000818:Animals; D001692:Biological Transport; D001921:Brain / Q000503:physiopathology; D002118:Calcium / Q000378:metabolism*; D002470:Cell Survival; D002544:Cerebral Infarction / Q000473:pathology; D002546:Ischemic Attack, Transient / Q000378:metabolism* / Q000473:pathology / Q000503:physiopathology; D008564:Membrane Potentials; D051379:Mice; D018345:Mice, Knockout; D009474:Neurons / Q000473:pathology; D018696:Neuroprotective Agents / Q000378:metabolism; D018408:Patch-Clamp Techniques; D019831:Sodium-Calcium Exchanger / Q000235:genetics / Q000378:metabolism / Q000502:physiology*
D018696:Neuroprotective Agents; C491739:Slc8a2 protein, mouse; D019831:Sodium-Calcium Exchanger; D002118:Calcium