Premium
Role of Na + ‐H + and Na + ‐Ca 2+ exchange in hypoxia‐related acute astrocyte death
Author(s) -
Bondarenko Alexander,
Svichar Nataliya,
Chesler Mitchell
Publication year - 2004
Publication title -
glia
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.954
H-Index - 164
eISSN - 1098-1136
pISSN - 0894-1491
DOI - 10.1002/glia.20107
Subject(s) - astrocyte , ouabain , calcium , amiloride , biophysics , hypoxia (environmental) , sodium calcium exchanger , biology , chemistry , sodium , medicine , microbiology and biotechnology , endocrinology , biochemistry , oxygen , central nervous system , organic chemistry
Cultured astrocytes do not succumb to hypoxia/zero glucose for up to 24 h, yet astrocyte death following injury can occur within 1 h. It was previously demonstrated that astrocyte loss can occur quickly when the gaseous and interstitial ionic changes of transient brain ischemia are simulated: After a 20–40‐min exposure to hypoxic, acidic, ion‐shifted Ringer (HAIR), most cells died within 30 min after return to normal saline (i.e., “reperfusion”). Astrocyte death required external Ca 2+ and was blocked by KB‐R7943, an inhibitor of reversed Na + ‐Ca 2+ exchange, suggesting that injury was triggered by a rise in [Ca 2+ ] i . In the present study, we confirmed the elevation of [Ca 2+ ] i during reperfusion and studied the role of Na + ‐Ca 2+ and Na + ‐H + exchange in this process. Upon reperfusion, elevation of [Ca 2+ ] i was detectable by Fura‐2 and was blocked by KB‐R7943. The low‐affinity Ca 2+ indicator Fura‐FF indicated a mean [Ca 2+ ] i rise to 4.8 ± 0.4 μM. Loading astrocytes with Fura‐2 provided significant protection from injury, presumably due to the high affinity of the dye for Ca 2+ . Injury was prevented by the Na + ‐H + exchange inhibitors ethyl isopropyl amiloride or HOE‐694, and the rise of [Ca 2+ ] i at the onset of reperfusion was blocked by HOE‐694. Acidic reperfusion media was also protective. These data are consistent with Na + loading via Na + ‐H + exchange, fostering reversal of Na + ‐Ca 2+ exchange and cytotoxic elevation of [Ca 2+ ] i . The results indicate that mechanisms involved in pH regulation may play a role in the fate of astrocytes following acute CNS injuries. © 2004 Wiley‐Liss, Inc.