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Na + ‐Ca 2+ exchanger mediates Ca 2+ influx during anoxia in mammalian central nervous system white matter
Author(s) -
Stys Peter K.,
Waxman Stephen G.,
Ransom Bruce R.
Publication year - 1991
Publication title -
annals of neurology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 4.764
H-Index - 296
eISSN - 1531-8249
pISSN - 0364-5134
DOI - 10.1002/ana.410300309
Subject(s) - bepridil , white matter , chemistry , central nervous system , biophysics , sodium calcium exchanger , tetrodotoxin , intracellular , calcium , endocrinology , biochemistry , biology , medicine , verapamil , organic chemistry , magnetic resonance imaging , radiology
White matter of the mammalian central nervous system suffers irreversible injury after prolonged anoxia, which can result in severe neurological impairment. This type of injury is critically dependent on Ca 2+ influx into cells. We present evidence that the Na + , Ca 2+ exchanger mediates the majority of the damaging Ca 2+ influx into cells during anoxia in white matter. Anoxic injury was studied in the isolated rat optic nerve, and functional recovery was monitored using the compound action potential. Blockers of voltage‐gated Na + channels (tetrodotoxin and saxitoxin) significantly improved recovery, as did perfusion with zeroNa + solution; both maneuvers would prevent intracellular [Na + ] from rising and thus prevent Ca 2+ influx by inhibiting reverse operation of the Na + , Ca 2+ exchanger. Direct pharmacological blockade of the Na + , Ca 2+ exchanger during anoxia with bepridil or benzamil also significantly improved recovery. These findings suggest that reverse operation of the Na + , Ca 2+ exchanger during anoxia is a critical mechanism of Ca 2+ influx and subsequent white matter injury.