Imaging the Hierarchical Ca2+ Signalling System in HeLa Cells

J Physiol. 1997 Mar 1;499 ( Pt 2)(Pt 2):307-14. doi: 10.1113/jphysiol.1997.sp021928.


1. Confocal microscopy was used to investigate hormone-induced subcellular Ca2+ release signals from the endoplasmic reticulum (ER) in a prototype non-excitable cell line (HeLa cells). 2. Histamine application evoked two types of elementary Ca2+ signals: (i) Ca2+ blips arising from single ER Ca2+ release channels (amplitude, 30 nM; lateral spreading, 1.3 microns); (ii) Ca2+ puffs resulting from the concerted activation of several Ca2+ blips (amplitude, 170 nM; spreading, 4 microns). 3. Ca2+ waves in the HeLa cells arose from a variable number of initiation sites, but for individual cells, the number and subcellular location of the initiation sites were constant. The kinetics and amplitude of global Ca2+ signals were directly proportional to the number of initiation sites recruited. 4. Reduction of the feedback inherent in intracellular Ca2+ release caused saltatoric Ca2+ waves, revealing the two principal steps underlying wave propagation: diffusion and regeneration. Threshold stimulation evoked abortive Ca2+ waves, caused by the limited recruitment of Ca2+ puffs. 5. The hierarchy of Ca2+ signalling events, from fundamental levels (blips) to intermediate levels (puffs) to Ca2+ waves, is a prototype for Ca2+ signal transduction for non-excitable cells, and is also analogous to the Ca2+ quarks, Ca2+ sparks and Ca2+ waves in cardiac muscle cells.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Aniline Compounds
  • Calcium / physiology*
  • Evoked Potentials
  • Fluorescent Dyes
  • HeLa Cells
  • Histamine / pharmacology
  • Humans
  • Kinetics
  • Microscopy, Confocal
  • Phosphatidylinositols / metabolism
  • Signal Transduction*
  • Xanthenes


  • Aniline Compounds
  • Fluorescent Dyes
  • Phosphatidylinositols
  • Xanthenes
  • Fluo-3
  • Histamine
  • Calcium