FCCP releases Ca2+ from a non-mitochondrial store in an identified Helisoma neuron

The proton ionophore FCCP was evaluated for use as a selective blocker of mitochondrial Ca2+ sequestration in identified Helisoma neurons in vitro. By use of the Ca2+ indicator fura-2, it was found that application of FCCP evoked a gradual increase in cell body [Ca2+]i that reached a level approximately 3-fold higher than baseline after 60 min. Moreover, FCCP released Ca2+ even when added after mitochondrial stores of Ca2+ had previously been emptied by an alternate method. From these and other experiments, it is concluded that FCCP, in addition to its recognized effect on mitochondrial Ca2+ sequestration, also releases Ca2+ from a non-mitochondrial store and is, therefore, unsuitable for use in an intact neuron to selectively inactivate mitochondrial Ca2+ uptake.