Oscillatory behavior in numerous biological systems has been recognized for many years. Some of the most striking examples are the oscillations in membrane potential seen in neuronal and cardiac cells, but similar oscillations are also seen in a number of secretory cells such as pancreatic l3-cells. Furthermore, it is now clear that in many instances these fluctuations in membrane potential are accompanied by oscillations in the concentration of intracellular free ionized calcium ([Ca2+] j) resulting from Ca2+ influx via voltage-sensitive Ca2+ channels.

In contrast, Ca2+ responses in non-excitable cells are generated via very different mechanisms and, until recently, were not thought to oscillate. In response to a stimulus there is usually an initial increase in [Ca2+] j resulting from release of Ca2+ from intracellular stores.[Ca2+] j then falls to a lower but still elevated level that can be sustained for many minutes provided that extracellular Ca2+ is present. One of the first demonstrations that Ca2+ oscillations can occur in non-excitable cells was a study by Cobbold and colleagues using hepatocytes injected with the Ca2+-sensitive photoprotein aequorin (163). In the same year Yada et al (166) showed, using Ca2+-selec tive microelectrodes, that [Ca2+] j oscillates in cultured epithelial cells. This raised the intriguing possibility that Ca2+ signals in non-excitable cells could be frequency, rather than simply amplitude, encoded as had been assumed up until then. With the advent of fluorescent probes for intracellular Ca2+[in particular the ratiometric dye fura-2 (48)] and techniques for monitoring [Ca2+] j at the single-cell level, it is now apparent that fluctuations or