Local influence of mitochondrial calcium transport in retinal amacrine cells

Abstract

Ca2+-dependent synaptic transmission from retinal amacrine cells is thought to be initiated locally at dendritic processes. Hence, understanding the spatial and temporal impact of Ca2+ transport is fundamental to understanding how amacrine cells operate. Here, we provide the first examination of the local effects of mitochondrial Ca2+ transport in neuronal processes. By combining mitochondrial localization with measurements of cytosolic Ca2+, the local impacts of mitochondrial Ca2+ transport for two types of Ca2+ signals were investigated. Disruption of mitochondrial Ca2+ uptake with carbonyl cyanide 4-(trifluoromethoxy) phenylhydrazone (FCCP) produces cytosolic Ca2+ elevations. The amplitudes of these elevations decline with distance from mitochondria suggesting that they are related to mitochondrial Ca2+ transport. The time course of the FCCP-dependent Ca2+ elevations depend on the availability of ER Ca2+ and we provide evidence that Ca2+ is released primarily via nearby ryanodine receptors. These results indicate that interactions between the ER and mitochondria influence cytosolic Ca2+ in amacrine cell processes and cell bodies. We also demonstrate that the durations of glutamate-dependent Ca2+ elevations are dependent on their proximity to mitochondria in amacrine cell processes. Consistent with this observation, disruption of mitochondrial Ca2+ transport alters the duration of glutamate-dependent Ca2+ elevations near mitochondria but not at sites more than 10 microm away. These results indicate that mitochondria influence local Ca2+-dependent signaling in amacrine cell processes.