The inositol 1,4,5-trisphosphate/calcium (IP 3 /Ca 2+ ) signaling pathway transmits information on the concentration of extracellular agonists of plasma membrane receptors to intracellular targets by dynamic changes of the cytosolic Ca 2+ concentration. In particular, Ca 2+ spike sequences have attracted attention of biophysical modeling in recent decades. We investigate spike sequences with regard to the information they provide on spike generation and feedbacks shaping spikes and interspike intervals (ISIs). The timing of spikes within a cell is random because each ISI has a large stochastic component. Cell-to-cell variability of the average ISI of individual cells in response to identical stimulation is very large. That is difficult to reconcile with the signal transmission function of the pathway. We report on cell-specific spike sequence properties and general properties, which are not subject to cell variability. The moment relation between standard deviation and average of the ISI distribution is highly conserved. The concentration response relation of stimulation has cell-specific and general parameters. It indicates possibilities for modes of information transmission. Information on feedbacks acting during spike sequences can be found in the second moments of ISI and amplitude distributions. The moment relation indicates the time scale of recovery from the negative feedback which terminates spikes. ISI-amplitude anti-correlation indicates additional negative feedback acting during this recovery. Both together suggest that spike initiation and amplitude are determined by different release channel populations. All general properties are related to noise and fluctuations. We suggest stochastic modeling concepts taking them into account.
Martin Falcke (Sun,) studied this question.