Fast Diffusion of Bound Ca 2+ : Analytical and Experimental Characterization of One- and Two-Dimensional Traveling Waves
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Reaction–diffusion (RD) systems play a fundamental role in numerous biochemical and biophysical processes. Here, we present a novel analytical framework for solving RD equations by applying the Wentzel–Kramers–Brillouin–Jeffreys (WKBJ) formalism to Ca 2+ nanodomains generated by individual membrane channels, a widely used paradigm for intracellular Ca 2+ signaling. Previous models have primarily focused on stationary Ca 2+ nanodomains while neglecting diffusion and saturation of intracellular Ca 2+ buffers and sensors. In contrast, we derive analytical solutions without these simplifying assumptions.
Our analysis demonstrates that sustained Ca 2+ influx generates continuously expanding distributions of free Ca 2+ , whereas Ca 2+ -bound buffers and sensors propagate as traveling waves. These predictions are supported experimentally by measurements of one-dimensional fluorescence profiles produced by single-channel activity and two-dimensional profiles generated by whole-cell Ca 2+ currents. The analytical framework developed here readily extends Michaelis–Menten-type kinetics to reaction–diffusion systems and may therefore be broadly applicable to biochemical and biophysical processes in which diffusion cannot be neglected.
Significance Statement
We present a novel analytical approach that combines Michaelis–Menten kinetics with diffusion through the Wentzel–Kramers–Brillouin–Jeffreys (WKBJ) formalism. The resulting closed-form solutions predict that free Ca 2+ remains localized near active channels, whereas Ca 2+ -bound buffers and sensors propagate through the cytoplasm as traveling waves. Consequently, intracellular signaling may depend not only on local Ca 2+ elevations but also on the propagation of mobile Ca 2+ -bound species. These theoretical predictions are validated experimentally in both one-dimensional and two-dimensional neuronal preparations.