Abstract
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 Ca2+ influx into cells. We present evidence that the Na+,Ca2+ exchanger mediates the majority of the damaging Ca2+ 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 zero-Na+ solution; both maneuvers would prevent intracellular [Na+] from rising and thus prevent Ca2+ influx by inhibiting reverse operation of the Na+,Ca2+ exchanger. Direct pharmacological blockade of the Na+,Ca2+ exchanger during anoxia with bepridil or benzamil also significantly improved recovery. These findings suggest that reverse operation of the Na+,Ca2+ exchanger during anoxia is a critical mechanism of Ca2+ influx and subsequent white matter injury.
Sign-in/Register to access full text options 
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a callDisclaimer: All third-party content on this website/platform is and will remain the property of their respective owners and is provided on "as is" basis without any warranties, express or implied. Use of third-party content does not indicate any affiliation, sponsorship with or endorsement by them. Any references to third-party content is to identify the corresponding services and shall be considered fair use under The CopyrightLaw.
