Ca 2+ marks: Miniature calcium signals in single mitochondria driven by ryanodine receptors

Propagation of cytosolic Ca(2+) (Ca(2+)(c)) signals to the mitochondria is believed to be supported by a local communication between Ca(2+) release channels and adjacent mitochondrial Ca(2+) uptake sites, but the signaling machinery has not been explored at the level of elementary Ca(2+) release events. Here, we demonstrate that Ca(2+)(c) sparks mediated by ryanodine receptors are competent to elicit miniature mitochondrial matrix Ca(2+) signals that we call "Ca(2+) marks." Ca(2+) marks are restricted to single mitochondria and typically last less than 500 ms. The decay of Ca(2+) marks relies on extrusion of Ca(2+) from the mitochondria through the Ca(2+) exchanger, whereas Ca(2+)(c) sparks decline primarily by diffusion. Mitochondria also appear to have a direct effect on the properties of Ca(2+)(c) sparks, because inhibition of mitochondrial Ca(2+) uptake results in an increase in the frequency and duration of Ca(2+)(c) sparks. Thus, a short-lasting opening of a cluster of Ca(2+) release channels can yield activation of mitochondrial Ca(2+) uptake, and the competency of mitochondrial Ca(2+) handling may be an important determinant of cardiac excitability through local feedback control of elementary Ca(2+)(c) signals.