Ca2+ marks:: Miniature calcium signals in single mitochondria driven by ryanodine receptors

Propagation of cytosolic [Ca2+] ([Ca2+]C) signals to the mitochondria is believed to be supported by a local communication between Ca2+ release channels and adjacent mitochondrial Ca2+ uptake sites, but the signaling machinery has not been explored at the level of elementary Ca2+ release events. Here, we demonstrate that [Ca2+]c sparks mediated by ryanodine receptors are competent to elicit miniature mitochondrial matrix [Ca2+] signals that we call "Ca2+ marks." Ca2+ marks are restricted to single mitochondria and typically last less than 500 ms. The decay of Ca2+ marks relies on extrusion of Ca2+ from the mitochondria through the Ca2+ exchanger, whereas [Ca2+], sparks decline primarily by diffusion. Mitochondria also appear to have a direct effect on the properties of [Ca2+]c sparks, because inhibition of mitochondrial Ca2+ uptake results in an increase in the frequency and duration of [Ca2+]c sparks. Thus, a short-lasting opening of a cluster of Ca2+ release channels can yield activation of mitochondrial Ca2+ uptake, and the competency of mitochondrial Ca2+ handling may be an important determinant of cardiac excitability through local feedback control of elementary [Ca2+]c signals.