Protection of ischaemic synaptosomes from calcium overload by addition of exogenous lactate.
In depolarised anoxic synaptosomes, in which lactate production was significantly raised compared with normoxic conditions, calcium uptake, net acetylcholine release, and the intrasynaptosomal calcium concentration were all significantly lowered. In contrast, lactate production in synaptosomes incubated under aglycaemic- and ischaemic-type conditions was significantly lower and basal calcium uptake, acetylcholine release, and intrasynaptosomal calcium concentration were elevated compared with normoxia. In addition, the increase in intrasynaptosomal calcium concentration under the ischaemic-type condition appeared to be greater than could be accounted for by the rise in calcium uptake alone. Intrasynaptosomal pH reflected the lactate production under each condition investigated. Addition of exogenous lactate to normoxic synaptosomes mimicked the effects observed in anoxia, suggesting that lactate itself may have blocked the calcium uptake, inhibiting the rise in intrasynaptosomal calcium and acetylcholine release occurring in depolarised anoxic synaptosomes. When lactate was added to ischaemic synaptosomes, the large rise in intrasynaptosomal calcium concentration, calcium uptake, and acetylcholine release were decreased, suggesting that lactate may have a protective role in preventing cell death by calcium overload under ischaemic-type conditions. Evidence is presented to suggest that the effect of L-lactate was due to the lactate moiety itself rather than the associated acidosis.
Boakye
P
P
Department of Biochemistry, St. Bartholomew's Hospital Medical College, University of London, England.
White
E J
EJ
Clark
J B
JB
D000109:Acetylcholine / Q000378:metabolism; D000818:Animals; D002545:Brain Ischemia / Q000378:metabolism*; D002118:Calcium / Q000378:metabolism*; D006863:Hydrogen-Ion Concentration; D000860:Hypoxia / Q000378:metabolism; D007773:Lactates / Q000494:pharmacology*; D019344:Lactic Acid; D008297:Male; D011189:Potassium Chloride / Q000494:pharmacology; D051381:Rats; D011919:Rats, Inbred Strains; D012016:Reference Values; D013574:Synaptosomes / Q000378:metabolism*
D007773:Lactates; D019344:Lactic Acid; D011189:Potassium Chloride; D000109:Acetylcholine; D002118:Calcium