The role of mitochondria in presynaptic calcium handling at a ribbon synapse

Mitochondria are thought to be important in clearing calcium from synaptic terminals. It is unclear, however, whether the principal role of mitochondria in presynaptic calcium handling is to take up Ca2+ directly or to fuel Ca2+ removal by other mechanisms. We used patch clamp techniques and fluorescence imaging to examine calcium clearance mechanisms, including mitochondrial uptake, in single synaptic terminals of retinal bipolar neurons. We found that extrusion through the ATP-dependent Ca2+ pump of the plasma membrane is the dominant form of Ca2+ removal in the synaptic terminal. Calcium uptake into mitochondria was sometimes evident with large Ca2+ loads but was consistently observed only when plasma membrane extrusion was inhibited. We conclude that mitochondria act primarily as an energy source in clearance of Ca2+ from bipolar cell synaptic terminals.