Twenty Years of Calcium Imaging: Cell Physiology to Dye For

Variance and dyssynchrony. The conditions of SR Ca²⁺ load heterogeneity (and other conditions of triggering heterogeneity) can lead to dyssynchronous activation of Ca²⁺ sparks. Here, a mathematical model reveals how increasingly dyssynchronous SR Ca²⁺ release may affect the [Ca²⁺]_i transient and fluctuations of [Ca²⁺]_i. A. Nearly synchronous Ca²⁺ release and a [Ca²⁺]_i transient over the period of one second. B. Mildly dyssynchronous Ca²⁺ spark activation (same number of Ca²⁺ sparks) slows the time-to-peak [Ca²⁺]_i transient, decreases the peak [Ca²⁺]_i level, and is associated with the development of [Ca²⁺]_i noise. C. Severely dyssynchronous SR Ca²⁺ release produces an even slower rise and smaller peak of the [Ca²⁺]_i transient and this is accompanied by even more [Ca²⁺]_i signaling “noise.” The same number of Ca²⁺ sparks is activated in panels A, B, and C. D. The time course of the standard deviation is plotted as a function of time (ms) normalized by the mean [Ca²⁺]_i. E. The integral of the signals in D.