How does intracellular Ca2+ oscillate: by chance or by the clock?

Ca(2+) oscillations have been considered to obey deterministic dynamics for almost two decades. We show for four cell types that Ca(2+) oscillations are instead a sequence of random spikes. The standard deviation of the interspike intervals (ISI) of individual spike trains is similar to the average ISI; it increases approximately linearly with the average ISI; and consecutive ISI are uncorrelated. Decreasing the effective diffusion coefficient of free Ca(2+) using Ca(2+) buffers increases the average ISI and the standard deviation in agreement with the idea that individual spikes are caused by random wave nucleation. Array enhanced coherence resonance (AECR) leads to regular Ca(2+) oscillations with small standard deviation of ISI.