J. Gleitz et al., ANAEROBIC GLYCOLYSIS AND POSTANOXIC RECOVERY OF RESPIRATION OF RAT CORTICAL SYNAPTOSOMES ARE REDUCED BY SYNAPTOSOMAL SODIUM LOAD, Brain research, 611(2), 1993, pp. 286-294
Synaptosomes of rat cerebral cortex were used to study the effect of v
eratridine-induced Na+ load on postanoxic recovery of respiration and
on aerobic and anaerobic ATP turnover, calculated from rates of oxygen
consumption and lactate production. Non-stimulated synaptosomes: afte
r onset of anoxia lactate synthesis of synaptosomes rose immediately f
rom 0.8 to 17.7 nmol lactate/min/mg protein indicating an anaerobic AT
P turnover of 17.7 nmol ATP/min/mg protein. This value accounts for 80
% of ATP synthesized during oxygenated conditions and seems to cover t
he energetic demand of anoxic synaptosomes. This assumption was suppor
ted by linearity of lactate production throughout anoxia (90 min), by
unaffected synaptosomal integrity and by complete recovery of postanox
ic respiration after 90 min of anoxia. Stimulated synaptosomes: stimul
ation of oxygenated synaptosomes with 10(-5) mol/l veratridine enhance
d ATP turnover 5-fold, due to activation of Na+/K+ ATPase, as a result
of veratridine-induced Na+ influx. Consequently, if not limited in ca
pacity, anaerobic ATP synthesis should be enhanced after addition of v
eratridine during anoxia. However, the opposite effect was observed. V
eratridine reduced anaerobic glycolysis in a concentration-dependent m
anner. This inhibitory effect could be prevented by tetrodotoxin appli
ed 5 min prior to veratridine. Inhibition of anaerobic glycolysis was
independent of extrasynaptosomal glucose (1-30 mmol/l) and Ca2+ concen
tration (Ca2+-free and 1.2 mmol/l Ca2+). Veratridine stimulation of an
oxic synaptosomes reduced also the recovery of postanoxic respiration.
The data indicate that Na+ load inhibits anaerobic ATP synthesis, the
only energy source during anaerobic conditions. To our knowledge, inh
ibition of anaerobic glycolysis due to increased Na+ influx has not be
en shown so far.