A Reevaluation of the Role of Mitochondria in Neuronal Ca2+ Homeostasis
Version of Record online: 19 NOV 2002
Journal of Neurochemistry
Volume 66, Issue 1, pages 403–411, January 1996
How to Cite
Budd, S. L. and Nicholls, D. G. (1996), A Reevaluation of the Role of Mitochondria in Neuronal Ca2+ Homeostasis. Journal of Neurochemistry, 66: 403–411. doi: 10.1046/j.1471-4159.1996.66010403.x
- Issue online: 19 NOV 2002
- Version of Record online: 19 NOV 2002
- Received May 15, 1995; revised manuscript received August 9, 1995; accepted August 9, 1995.
- Granule cell;
Abstract: The ability of mitochondrial Ca2+ transport to limit the elevation in free cytoplasmic Ca2+ concentration in neurones following an imposed Ca2+ load is reexamined. Cultured cerebellar granule cells were monitored by digital fura-2 imaging. Following KCI depolarization, addition of the protonophore carbonylcyanide m-chlorophenylhydrazone (CCCP) to depolarize mitochondria released a pool of Ca2+ into the cytoplasm in both somata and neurites. No CCCP-releasable pool was found in nondepolarized cells. Although the KCI-evoked somatic and neurite Ca2+ concentration elevations were enhanced when CCCP was present during KCI depolarization, this was associated with a collapsed ATP/ADP ratio. In the presence of the ATP synthase inhibitor oligomycin, glycolysis maintained high ATP/ADP ratios for at least 10 min. The further addition of the mitochondrial complex I inhibitor rotenone led to a collapse of the mitochondrial membrane potential, monitored by rhodamine-123, but had no effect on ATP/ADP ratios. In the presence of rotenone/oligomycin, no CCCP-releasable pool was found subsequent to KCI depolarization, consistent with the abolition of mitochondrial Ca2+ transport; however, paradoxically the KCI-evoked Ca2+ elevation is decreased. It is concluded that the CCCP-induced increase in cytoplasmic Ca2+ response to KCI is due to inhibition of nonmitochondrial ATP-dependent transport and that mitochondrial Ca2+ transport enhances entry of Ca2+, perhaps by removing the cation from cytoplasmic sites responsible for feedback inhibition of voltage-activated Ca2+ channel activity.