Calcium oscillates in and out!

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 fura-C₁₈ to show that activation of CaRs produces local oscillations in the extracellular Ca²⁺ concentration. Since the CaRs and PMCAs appear to reside in specific membrane microdomains, the authors suggest that local extracellular Ca²⁺ oscillations in these regions help to reinforce the intracellular oscillations.