title: Mechanisms of injury-induced calcium entry into peripheral nerve myelinated axons: role of reverse sodium-calcium exchange.
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 microM) 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 microM) reduced significantly the Ca content of anoxic axons although mitochondrial Ca remained at anoxic levels. Nifedipine (10 microM), 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.
authors.affiliation: Department of Anesthesiology, Albert Einstein College of Medicine, Montefiore Medical Center, Bronx, New York 10467, USA.
authors.forename: E J
authors.initials: EJ
authors.lastname: Lehning
authors.forename: R
authors.initials: R
authors.lastname: Doshi
authors.forename: N
authors.initials: N
authors.lastname: Isaksson
authors.forename: P K
authors.initials: PK
authors.lastname: Stys
authors.forename: R M
authors.initials: RM
authors.lastname: LoPachin
mesh_terms: D000818:Animals; D001369:Axons / Q000378:metabolism*; D015764:Bepridil / Q000494:pharmacology; D002118:Calcium / Q000378:metabolism* / Q000494:pharmacology; D002121:Calcium Channel Blockers / Q000494:pharmacology; D002352:Carrier Proteins / Q000037:antagonists & inhibitors / Q000502:physiology*; D015687:Cell Hypoxia; D066298:In Vitro Techniques; D008297:Male; D009413:Nerve Fibers, Myelinated / Q000378:metabolism*; D010100:Oxygen / Q000378:metabolism; D010477:Perfusion; D051381:Rats; D017207:Rats, Sprague-Dawley; D012016:Reference Values; D012964:Sodium / Q000494:pharmacology; D026941:Sodium Channel Blockers; D019831:Sodium-Calcium Exchanger; D013979:Tibial Nerve
chemical_list: D002121:Calcium Channel Blockers; D002352:Carrier Proteins; D026941:Sodium Channel Blockers; D019831:Sodium-Calcium Exchanger; D015764:Bepridil; D012964:Sodium; D010100:Oxygen; D002118:Calcium