Dominant role of mitochondria in protection against a delayed neuronal Ca2+ overload induced by endogenous excitatory amino acids following a glutamate pulse.
The objective of this study was to evaluate the contribution of mitochondria to the clearance of Ca2+ loads induced by glutamate or 25 mM K+ pulses. The mitochondrial Ca2+ uptake was suppressed by application of 0.5 microM antimycin A or 3-5 mM NaCN in combination with 2.5 micrograms/ml oligomycin. In most cells such treatments both in the presence and in the absence of external Na+ failed to abolish the early fast phase of [Ca2+]i recovery following a 1-min 100 microM glutamate pulse. However, the late slow phase of [Ca2+]i recovery in the presence of mitochondrial poisons was transformed into a delayed [Ca2+]i elevation culminating in the neuronal Ca2+ overload. Suppression of the Na+/Ca2+ exchange caused by glutamate-induced [Na+]i elevation promoted the development of delayed Ca2+ increase. Under identical conditions, the high [Ca2+]i transient induced by 25 mM K+ was never accompanied by a delayed Ca2+ elevation. The glutamate-induced delayed Ca2+ increase could be readily abolished by the removal of external Ca2+ or by application in the post-glutamate period of the antagonist of NMDA receptors, 100-200 microM AP-5. The results obtained suggest that mitochondria play a dominant role in the protection against the neuronal Ca2+ overload induced by endogenous excitatory amino acids released in response to a short-term glutamate challenge.
Khodorov
B
B
Institute of General Pathology and Pathophysiology, Russian Academy of Medical Sciences, Moscow, Russian Federation. rans@rans.msk.ru
Pinelis
V
V
Storozhevykh
T
T
Vergun
O
O
Vinskaya
N
N
D000818:Animals; D000968:Antimycin A / Q000378:metabolism; D002118:Calcium / Q000378:metabolism*; D002478:Cells, Cultured; D002531:Cerebellum / Q000166:cytology / Q000187:drug effects; D018846:Excitatory Amino Acids / Q000494:pharmacology*; D005971:Glutamates / Q000494:pharmacology*; D008928:Mitochondria / Q000187:drug effects / Q000378:metabolism*; D009474:Neurons / Q000187:drug effects / Q000378:metabolism*; D009840:Oligomycins / Q000378:metabolism; D011188:Potassium / Q000494:pharmacology*; D051381:Rats; D017208:Rats, Wistar
D018846:Excitatory Amino Acids; D005971:Glutamates; D009840:Oligomycins; D000968:Antimycin A; D011188:Potassium; D002118:Calcium