Ca2+ waves, Ca2+ oscillations, local Ca2+spikes and puffs – intracellular Ca2+ signalling is very complex. Well, it gets worse: Annunziata De Luisi and Aldebaran Hofer now reveal that extracellular Ca2+ levels oscillate too (see p. 1527). They show that stimulation of the extracellular Ca2+ receptor CaR (a G-protein-coupled receptor that monitors extracellular Ca2+)produces oscillations in intracellular Ca2+ levels in clusters of adjacent HEK293 cells. Since the oscillations are unaffected by gap junction inhibitors, the authors speculated that they might be transmitted by release of Ca2+ through plasma membrane Ca2+ pumps (PMCAs) and its activation of CaRs on neighbouring cells. Indeed, De Luisi and Hofer demonstrate that PMCA inhibitors (e.g. HgCl2) block the response,as do buffers that maintain extracellular Ca2+ at a constant level(e.g. BAPTA free acid). They also use the near-membrane Ca2+ probe...

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