A model-independent algorithm to derive Ca2+ fluxes underlying local cytosolic Ca2+ transients

ALEJANDRA C VENTURA; LUCIANA BRUNO; ANGELO DEMURO; IAN PARKER; SILVINA PONCE DAWSON

Dresden, Germany

Conferencia; European Conference on Mathematical and Theoretical Biology; 2005

European Society for Mathematical and Theoretical Biology

Local intracellular Ca$^{2+}$ signals result from Ca$^{2+}$ flux into the cytosol through individual channels or clusters of channels. To gain a mechanistic understanding of these events we need to know the magnitude and spatial distribution of the underlying Ca$^{2+}$ flux. However, this is difficult to infer from fluorescence Ca$^{2+}$ images because the distribution of Ca$^{2+}$-bound dye is affected by poorly characterized processes including diffusion of Ca$^{2+}$ ions, their binding to mobile and immobile buffers and sequestration by Ca$^{2+}$ pumps. Several methods have previously been proposed to derive Ca$^{2+}$ flux from fluorescence images, but all require explicit knowledge or assumptions regarding these processes. We now present a novel algorithm that requires few assumptions and is largely model-independent. By testing the algorithm with both numerically generated ``image´´ data and experimental images of sparklets resulting from Ca$^{2+}$ flux through individual voltage-gated channels, we show that it satisfactorily reconstructs the magnitude and time course of the underlying Ca$^{2+}$ currents.