Calcium waves and oscillations in networks of glial cells

Thomas Hoefer

Intracellular calcium transients play a central role in many signal transduction cascades. Recent experiments show that calcium signals can also propagate from one cell to another in a variety of cell populations; examples include hormone-evoked calcium oscillations in hepatocytes and glia-to-neuron signalling in response to neurotransmitters. The coupling mechanisms that can support such intercellular calcium signals remain unclear. Potential candidates are communication through gap junctions and paracrine signalling. In experiments with hormone-stimulated hepatocytes, one finds that isolated cells exhibit widely varying intrinsic oscillation frequencies but signal in unison in the intact, gap junction-coupled ensemble. To provide a mechanistic rationale for these observations, a mathematical model of intracellular calcium dynamics in hepatocytes is extended to the situation of coupled cells with gap junctional calcium diffusion. Potential sources of the frequency variability of calcium oscillations in individual cells are identified. Numerical simulations and bifurcation analysis are carried out to obtain insight into the synchronization properties of the model in the case of two coupled, heterogeneous cells. Gap junctional calcium fluxes are found effective in rapidly synchronizing calcium oscillations, and an experimentally testable estimate is given for the junctional coupling coefficient required. Comparison of the model behaviour to experimental data obtained with a number of experimental protocols yields further insight into this mechanism of intercellular signalling.

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