@article {Pivovarova6372, author = {Natalia B. Pivovarova and Jarin Hongpaisan and S. Brian Andrews and David D. Friel}, title = {Depolarization-Induced Mitochondrial Ca Accumulation in Sympathetic Neurons: Spatial and Temporal Characteristics}, volume = {19}, number = {15}, pages = {6372--6384}, year = {1999}, doi = {10.1523/JNEUROSCI.19-15-06372.1999}, publisher = {Society for Neuroscience}, abstract = {Several lines of evidence suggest that neuronal mitochondria accumulate calcium when the cytosolic free Ca2+concentration ([Ca2+]i) is elevated to levels approaching \~{}500 nm, but the spatial, temporal, and quantitative characteristics of net mitochondrial Ca uptake during stimulus-evoked [Ca2+]ielevations are not well understood. Here, we report direct measurements of depolarization-induced changes in intramitochondrialtotal Ca concentration ([Ca]mito) obtained by x-ray microanalysis of rapidly frozen neurons from frog sympathetic ganglia. Unstimulated control cells exhibited undetectably low [Ca]mito, but high K+depolarization (50 mm, 45 sec), which elevates [Ca2+]i to \~{}600 nm, increased [Ca]mito to 13.0 {\textpm} 1.5 mmol/kg dry weight; this increase was abolished by carbonyl cyanidep-(trifluoromethoxy) phenylhydrazone (FCCP). The elevation of [Ca]mito was a function of both depolarization strength and duration. After repolarization, [Ca]mito recovered to prestimulation levels with a time course that paralleled the decline in [Ca2+]i. Depolarization-induced increases in [Ca]mito were spatially heterogeneous. At the level of single mitochondria, [Ca]mito elevations depended on proximity to the plasma membrane, consistent with predictions of a diffusion model that considers radial [Ca2+]i gradients that exist early during depolarization. Within individual mitochondria, Ca was concentrated in small, discrete sites, possibly reflecting a high-capacity intramitochondrial Ca storage mechanism. These findings demonstrate that in situ Ca accumulation by mitochondria, now directly identified as the structural correlate of the {\textquotedblleft}FCCP-sensitive store,{\textquotedblright} is robust, reversible, graded with stimulus strength and duration, and dependent on spatial location.}, issn = {0270-6474}, URL = {https://www.jneurosci.org/content/19/15/6372}, eprint = {https://www.jneurosci.org/content/19/15/6372.full.pdf}, journal = {Journal of Neuroscience} }