Fura-2 antagonises calcium-induced calcium release

Cell Calcium. 2003 Jan;33(1):27-35. doi: 10.1016/s0143-4160(02)00179-3.


Calcium-induced calcium release (CICR) from the endoplasmic reticulum (ER) takes place through ryanodine receptors (RyRs) and it is often revealed by an increase of the cytosolic Ca(2+) concentration ([Ca(2+)](c)) induced by caffeine. Using fura-2-loaded cells, we find such an effect in bovine adrenal chromaffin cells, but not in cerebellar granule neurones or in HEK-293 cells. In contrast, a caffeine-induced [Ca(2+)](c) increase was clearly visible with either fluo-3 or cytosolic aequorin. Simultaneous loading with fura-2 prevented the [Ca(2+)](c) increase reported by the other Ca(2+) probes. Caffeine-induced Ca(2+) release was also measured by following changes of [Ca(2+)] inside the ER ([Ca(2+)](ER)) with ER-targeted aequorin in HEK-293 cells. Fura-2 loading did not modify Ca(2+) release from the ER. Thus, fura-2, but not fluo-3, antagonises the generation of the cytosolic Ca(2+) signal induced by activation of RyRs. Cytosolic Ca(2+) buffering and/or acceleration of Ca(2+) diffusion through the cytosol may contribute to these actions. Both effects may interfere with the generation of microdomains of high [Ca(2+)](c) near the ER release channels, which are essential for the propagation of the Ca(2+) wave through the cytosol. In any case, our results caution the use of fura-2 to study CICR.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Aequorin / pharmacology
  • Aniline Compounds / pharmacology
  • Animals
  • Animals, Newborn
  • Caffeine / pharmacology
  • Calcium / metabolism*
  • Calcium Signaling / physiology*
  • Cattle
  • Cells, Cultured
  • Chromaffin Cells / drug effects
  • Chromaffin Cells / metabolism
  • Cytosol / drug effects
  • Cytosol / metabolism*
  • Endoplasmic Reticulum / drug effects
  • Endoplasmic Reticulum / metabolism*
  • Eukaryotic Cells / drug effects
  • Eukaryotic Cells / metabolism*
  • Fura-2 / pharmacology
  • Humans
  • Neurons / drug effects
  • Neurons / metabolism
  • Protein Structure, Tertiary / drug effects
  • Protein Structure, Tertiary / physiology
  • Rats
  • Rats, Wistar
  • Ryanodine Receptor Calcium Release Channel / drug effects
  • Ryanodine Receptor Calcium Release Channel / metabolism
  • Xanthenes / pharmacology


  • Aniline Compounds
  • Ryanodine Receptor Calcium Release Channel
  • Xanthenes
  • Fluo-3
  • Caffeine
  • Aequorin
  • Calcium
  • Fura-2