A novel multi lines analysis tool of Ca2+ dynamics reveals the nonuniformity of Ca2+ propagation

Extracellular stimuli evoke a robust increase in the concentration of intracellular Ca²⁺ (Ca²⁺]_c) throughout the cell to trigger various cellular responses, such as gene expression and apoptosis. This robust expansion of Ca²⁺]_c is called Ca²⁺ propagation. To date, it is thought that intracellular second messengers, such as inositol 1,4,5-trisphosphate (IP₃) and intracellular Ca²⁺, and clusters of IP₃ receptors (IP₃Rs) regulate Ca²⁺ propagation. However, little is known about how the elevation in the Ca²⁺]_c spreads throughout the cell, especially in non-polar cell, including HeLa cell. In this study, we developed a novel multi lines analysis tool. This tool revealed that the velocity of Ca²⁺ propagation was inconstant throughout cell and local concentration of intracellular Ca²⁺ did not contribute to the velocity of Ca²⁺ propagation. Our results suggest that intracellular Ca²⁺ propagation is not merely the result of diffusion of intracellular Ca²⁺, and that, on the contrary, intracellular Ca²⁺ propagation seems to be regulated by more complicated processes.