Calcium encoding

Principle of calcium encoding. A schematics of intracellular calcium signaling and its equivalent from a calcium encoding perspective.

Calcium encoding (also referred to as Ca²⁺ encoding or calcium information processing) is an intracellular signaling pathway used by many cells to transfer, process and encode external information detected by the cell. In cell physiology, external information is often converted into intracellular calcium dynamics. The concept of calcium encoding explains how Ca²⁺ ions act as intracellular messengers, relaying information within cells to regulate their activity. Given the ubiquity of Ca²⁺ ions in cell physiology, Ca²⁺ encoding has also been suggested as a potential tool to characterize cell physiology in health and disease. The mathematical bases of Ca²⁺ encoding have been pioneered by work of Joel Keizer and Hans G. Othmer on calcium modeling in the 1990s and more recently they have been revisited by Eshel Ben-Jacob, Herbert Levine and co-workers.

AM, FM and AFM calcium encoding

Elementary modes of calcium encoding. AM, FM and AFM encoding Ca²⁺ oscillations correspond to analogous modulations in electronic communications.

Although elevations of Ca²⁺ are necessary for it to act as a signal, prolonged increases of the concentration of Ca²⁺ in the cytoplasm can be lethal for the cell. Thus cells avoid death usually delivering Ca²⁺ signals as brief transients - i.e. Ca²⁺ elevations followed by a rapid decay - or in the form of oscillations. In analogy with Information Theory, either the amplitude or the frequency or both features of these Ca2+ oscillations define the Ca²⁺ encoding mode. Therefore three classes of Ca²⁺ signals can be distinguished on the basis of their encoding mode:

• • AM encoding Ca²⁺ signals: when the strength of the stimuli is encoded by amplitude modulations of Ca²⁺ oscillations. In other words, stimuli of the same nature but of different strength are associated with different amplitudes of Ca²⁺ oscillations but the frequencies of these oscillations are similar;
  • FM encoding Ca²⁺ signals: when the strength of the stimuli is encoded by frequency modulations of Ca²⁺ oscillations. In other words, stimuli of the same nature but of different strength are associated with different frequencies of Ca²⁺ oscillations but the amplitudes of these oscillations are similar;
  • AFM encoding Ca²⁺ signals: when both AM and FM encoding modes coexist.

Experiments and biophysical modeling, show that the mode of calcium encoding varies from cell to cell, and that a given cell could even show different types of calcium encoding for different patho-physiological conditions. This could ultimately provide a crucial tool in medical diagnostics, to characterize, recognize and prevent diseases.

Mathematical aspects of calcium encoding

Calcium encoding can be mathematically characterized by biophysical models of calcium signaling. Phase plane and bifurcation analysis of these models, can reveal in fact how frequency and amplitude of calcium oscillations vary as a function of any parameter of the model. Occurrence of AM-, FM- or AFM-encoding can be assessed on the extension of the min-max range of amplitude and frequency of Ca²⁺ oscillations and the bifurcation structure of the system under study.

Stimulus integration. Only if the stimulus allows accumulation (i.e. integration) of IP₃ up to a certain threshold then a FM-encoding Ca²⁺ oscillation occurs.

A critical aspect of Ca²⁺ encoding revealed by modeling, is how it depends on the dynamics of the complex network of reactions of underlying Ca²⁺-mobilizing signals. This aspect can be addressed considering Ca²⁺ models that include both Ca²⁺ dynamics and the dynamics of Ca²⁺-mobilizing signals. One simple and biophysically realistic model of this kind is the ChI model, originally developed by Eshel Ben-Jacob and co-workers, for GPCR-mediated inositol 1,4,5 trisphospate (IP₃)-triggered Ca²⁺-induced Ca²⁺-release. The main conclusion of this study was that the dynamics of the Ca²⁺-mobilizing IP₃ signal is essentially AFM encoding with respect to the stimulus whereas Ca²⁺ oscillations can be either FM or AFM but not solely AM. It was argued that the AFM nature of the Ca²⁺-mobilizing IP₃ signal could represent the ideal solution to optimally translate pulsed or discontinuous extracellular signals into intracellular continuous-like Ca²⁺ oscillations.

Computational aspects

Calcium encoding can be confined within a single cell or involve cell ensembles and deploy essential computational tasks, such as stimulus integration or regulated activation of gene transcription. Moreover cells are often organized in networks, allowing intercellular propagation of calcium signaling. With this regard, the same mode of calcium encoding could be shared by different cells, providing synchronization or the functional basis to implement more complex computational tasks.

External links

• Cell Signaling Biology
• Prof. Eshel Ben-Jacob's homepage
• Prof. Herbert Levine's homepage
• Prof. Hugues Berry's homepage
• Dr. Vladislav Volman's homepage
• Dr. Maurizio De Pittà's homepage