Pk. Stys et Rm. Lopachin, MECHANISMS OF CALCIUM AND SODIUM FLUXES IN ANOXIC MYELINATED CENTRAL-NERVOUS-SYSTEM AXONS, Neuroscience, 82(1), 1998, pp. 21-32
Electron probe X-ray microanalysis was used to measure water content a
nd concentrations of elements (i.e. Na, K, Cl and Ca) in selected morp
hological compartments of rat optic nerve myelinated axons. Transaxole
mmal movements of Na+ and Ca2+ were modified experimentally and corres
ponding effects on axon element and water compositions were determined
under control conditions and following in vitro anoxic challenge. Als
o characterized were effects of modified ion transport on axon respons
es to postanoxia reoxygenation. Blockade of Na+ entry by tetrodotoxin
(1 mu M) or zero Na+/Li+-substituted perfusion reduced anoxic increase
s in axonal Na and Ca concentrations. Incubation with zero-Ca2+/EGTA p
erfusate prevented axoplasmic and mitochondrial Ca accumulation during
anoxia but did not affect Na increases or K losses in these compartme
nts. Inhibition of Na+-Ca2+ exchange with bepridil (30 mu M) selective
ly prevented increases in intra-axonal Ca, whereas neither nifedipine
(5 mu M) nor nimodipine (5 mu M) influenced the effects of anoxia on a
xonal Na, K or Ca. X-ray microanalysis also showed that prevention of
Na and Ca influx during anoxia obtunded severe elemental deregulation
normally associated with reoxygenation. Results of the present study s
uggest that during anoxia, Na+ enters axons mainly through voltage-gat
ed Na+ channels and that subsequent increases in axoplasmic Na+ are fu
nctionally coupled to extra-axonal Ca2+ import. Na-i(+)-dependent, Ca-
o(2+) entry is consistent with reverse operation of the axolemmal Na+-
Ca2+ exchanger and we suggest this route represents a primary mechanis
m of Ca2+ influx. Our findings also implicate a minor route of Ca2+ en
try directly through Na+ channels. (C) 1997 IBRO. Published by Elsevie
r Science Ltd.