Mechanisms of Injury-Induced Calcium Entry into Peripheral Nerve Myelinated Axons: Role of Reverse Sodium-Calcium Exchange
Version of Record online: 23 NOV 2002
Journal of Neurochemistry
Volume 66, Issue 2, pages 493–500, February 1996
How to Cite
Lehning, E. J., Doshi, R., Isaksson, N., Stys, P. K. and LoPachin, R. M. (1996), Mechanisms of Injury-Induced Calcium Entry into Peripheral Nerve Myelinated Axons: Role of Reverse Sodium-Calcium Exchange. Journal of Neurochemistry, 66: 493–500. doi: 10.1046/j.1471-4159.1996.66020493.x
- Issue online: 23 NOV 2002
- Version of Record online: 23 NOV 2002
- Received April 21, 1995; revised manuscript received July 31, 1995; accepted August 22, 1995.
- Peripheral nerve;
- Myelinated axons;
- Electron probe x-ray microanalysis;
- Na+-Ca2+ exchanger;
Abstract: To investigate the route of axonal Ca2+ entry during anoxia, electron probe x-ray microanalysis was used to measure elemental composition of anoxic tibial nerve myelinated axons after in vitro experimental procedures that modify transaxolemmal Na+ and Ca2+ movements. Perfusion of nerve segments with zero-Na+/Li+-substituted medium and Na+ channel blockade by tetrodotoxin (1 µM) prevented anoxia-induced increases in Na and Ca concentrations of axoplasm and mitochondria. Incubation with a zero-Ca2+/EGTA perfusate impeded axonal and mitochondrial Ca accumulation during anoxia but did not affect characteristic Na and K responses. Inhibition of Na+-Ca2+ exchange with bepridil (50 µM) reduced significantly the Ca content of anoxic axons although mitochondrial Ca remained at anoxic levels. Nifedipine (10 µM), an L-type Ca2+ channel blocker, did not alter anoxia-induced changes in axonal Na, Ca, and K. Exposure of normoxic control nerves to tetrodotoxin, bepridil, or nifedipine did not affect axonal elemental composition, whereas both zero-Ca2+ and zero-Na+ solutions altered normal elemental content characteristically and significantly. The findings of this study suggest that during anoxia, Na+ enters axons via voltage-gated Na+ channels and that subsequent increases in axoplasmic Na+ are coupled functionally to extraaxonal Ca2+ import. Intracellular Na+-dependent, extraaxonal Ca2+ entry is consistent with reverse operation of the axolemmal Na+-Ca2+ exchanger, and we suggest that this mode of Ca2+ influx plays a general role in peripheral nerve axon injury.