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

Proc Natl Acad Sci U S A. 2002 Feb 19;99(4):2380-5. doi: 10.1073/pnas.032423699.

Abstract

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.

Publication types

  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Animals
  • Calcium / metabolism*
  • Cell Line
  • Dose-Response Relationship, Drug
  • Microscopy, Confocal
  • Mitochondria / metabolism*
  • Mitochondria, Heart / metabolism*
  • Myocardium / cytology*
  • Rats
  • Rhodamines / pharmacology
  • Ryanodine / metabolism
  • Ryanodine / pharmacology*
  • Ryanodine Receptor Calcium Release Channel / metabolism*
  • Signal Transduction
  • Time Factors

Substances

  • Rhodamines
  • Ryanodine Receptor Calcium Release Channel
  • Ryanodine
  • Calcium