Stochastic events underlie Ca2+ signalling in neutrophils.

In order to probe the events which couple receptor occupancy to elevation of cytosolic free Ca2+ fast laser scanning of fluo3-loaded neutrophils was used to determine the timing of the initial phase of the Ca2+ response. This approach demonstrated that there was a measurable delay between the addition of stimulus and the onset of the cytosolic free Ca2+ signal which varied from cell to cell variable from 75 ms to greater than 1.5 s. The distribution of lag times was similar to that expected if the delay resulted from a series of obligatory stochastic processes. From the Poisson equation, a probability density function for the delays was generated which depended on n, the number of stochastic events in the series, and lambda, the stochastic rate for the events. The best fit between the data and theory was found to be for six stochastic steps in the series occurring with a stochastic rate similar to that expected for diffusion of known small molecular weight signalling molecules within the cell. We, therefore, propose that the delays in onset of the Ca2+ response in neutrophils were the result of sequence of diffusion steps, each with sufficiently small numbers of intracellular messenger molecules to generate stochastic behaviour.