1050 J. G. McGeown Exp Physiol 95.11 pp 1049–1060 Figure 1. Calcium ion spiral waves in Xenopus oocytes Three frames have been chosen from a movie of an oocyte to show how the wave patterns evolve over time. These spectacularly patterned signals were ﬁrst described by Lechleiter et al. (1991). Reproduced with permission of Professor James Lechleiter PhD: http://www.uthscsa.edu/csb/faculty/lechleiter.asp. What is so special about Ca2+ anyway? Before looking at Ca2+ imaging itself, I want to provide a very brief and ridiculously selective overview of the evidence pointing to the importance of Ca2+ signalling. Although free Ca2+ inside the cytosol is a very small percentage of total body Ca2+, most of which is found in bone mineral, it is a crucial cell signal in many cell types. Some of the earliest evidence for this came from experiments carried out in the 1880s on frog heart muscle by Sydney Ringer. He wanted to develop a salt solution suitable for in vitro studies on isolated tissues. Early experiments were promising, but subsequent attempts to repeat the work gave much less satisfactory results. Some detective work led to the discovery (Ringer, 1883) ‘that the saline solution which I had used’ (i.e. in the earlier successful study) ‘had not been prepared with distilled water, but with pipe water supplied by the New River Water Company . . . . . It is obvious therefore that the effects I had obtained are due to some of the inorganic constituents of the pipe water.’ It is generally accepted that Ringer’s technician was probably responsible for the initial oversight in using pipe water rather than distilled water, but the consequences were positive, since they demonstrated both that the heart could be kept beating and that this required some ingredient missing from saline prepared with distilled water (Miller, 2004). Ringer went on to determine which of the ‘inorganic constituents’ in pipe water was important and discovered that his artiﬁcial saline solution only supported consistent cardiac contractions when Ca2+ was present, suggesting that this was necessary for normal cell function (Fig. 2). By such serendipity knowledge is advanced. Figure 2. An early demonstration of the importance of Ca2+ for muscle contractility Changes in volume were recorded from an isolated frog ventricle perfused with blood or saline solutions (more detail on the technique and Ringer’s work is presented by Miller, 2004). Full contractions were only seen when Ca2+ was present in the perfusate. Figure reproduced with permission from Ringer (1883). C 2010 The Author. Journal compilation C 2010 The Physiological Society