Ca2+ 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.
Pacher
Pál
P
Department of Pathology, Anatomy, and Cell Biology, Thomas Jefferson University, Philadelphia, PA 19107, USA.
Thomas
Andrew P
AP
Hajnóczky
György
G
D000818:Animals; D002118:Calcium / Q000378:metabolism*; D002460:Cell Line; D004305:Dose-Response Relationship, Drug; D018613:Microscopy, Confocal; D008928:Mitochondria / Q000378:metabolism*; D008929:Mitochondria, Heart / Q000378:metabolism*; D009206:Myocardium / Q000166:cytology*; D051381:Rats; D012235:Rhodamines / Q000494:pharmacology; D012433:Ryanodine / Q000378:metabolism / Q000494:pharmacology*; D019837:Ryanodine Receptor Calcium Release Channel / Q000378:metabolism*; D015398:Signal Transduction; D013997:Time Factors
D012235:Rhodamines; D019837:Ryanodine Receptor Calcium Release Channel; D012433:Ryanodine; D002118:Calcium