Confocal imaging of subcellular Ca2+ concentrations using a dual-excitation ratiometric indicator based on green fluorescent protein

Sci STKE. 2002 Mar 26;2002(125):pl4. doi: 10.1126/stke.2002.125.pl4.

Abstract

Dual-excitation ratiometric dyes are excited alternately at two different wavelengths, but the emission is collected at a single fixed wavelength. Therefore, the pair of intensity measurements must be collected sequentially. Ratiometric-pericam is a fluorescent Ca(2+) indicator based on a chimeric fusion protein of circularly permuted green fluorescent protein and calmodulin. Upon binding to calcium, its excitation peak shifts from 415 nm to 494 nm. Ca(2+) imaging using ratiometric-pericam was thought to be inadequate to follow very fast Ca(2+) dynamics or Ca(2+) changes in highly motile cell samples; however, we describe a technique that allows high spatial and time resolution of images acquired with ratiometric-pericam. To obtain confocal images of Ca(2+) using ratiometric-pericam, we established a system in which two laser beams (excitation 408 nm and 488 nm) are alternated on every scanning line under the control of two acousto-optic tunable filters. This system increases the rate at which ratio measurements are done to 200 Hz, and provides confocal images at 1 to 10 Hz depending on the image size. The ratio images are free from noise caused by the fluctuation of laser power, because the system is equipped with a violet laser diode (408 nm) and a diode-pumped solid-state laser (488 nm), both of which are stable. We visualized the dynamic propagation of Ca(2+) waves from the cytosol to the nucleus and changes in Ca(2+) concentrations in motile mitochondria of HeLa cells. We demonstrate that this new confocal imaging system expands the range of potential applications of ratiometric-pericam and other dual-excitation ratiometric indicators.

MeSH terms

  • Calcium / metabolism*
  • Cell Nucleus / metabolism
  • Cytosol / metabolism
  • Diffusion
  • Fluorescent Dyes / analysis
  • Green Fluorescent Proteins
  • HeLa Cells
  • Humans
  • Indicators and Reagents / analysis
  • Luminescent Proteins / analysis*
  • Microscopy, Confocal / instrumentation
  • Microscopy, Confocal / methods*
  • Mitochondria / metabolism
  • Tumor Cells, Cultured

Substances

  • Fluorescent Dyes
  • Indicators and Reagents
  • Luminescent Proteins
  • Green Fluorescent Proteins
  • Calcium