Twenty Years of Calcium Imaging: Cell Physiology to Dye For

Effects of spatial heterogeneity of SR Ca²⁺content. A. Diagram of the cross-section of a cell with the SR Ca²⁺ release sites (or jSR or Ca²⁺ release “units”) represented as open circles. B. Time sequence (i–iv) of [Ca²⁺]_i images of control heart cell with normal Ca²⁺ load in the jSR represented as black filled circles. Ca²⁺ sparks occur at a low rate and do not trigger other Ca²⁺ sparks or Ca²⁺ waves. C. Time sequence of [Ca²⁺]_i images of a cell with global Ca²⁺ overload. The jSR sites with elevated Ca²⁺ content are represented as red filled circles. Ca²⁺ sparks can trigger neighboring jSR to produce a propagating wave of elevated [Ca²⁺]_i. D. Time sequence of [Ca²⁺]_i images of a cell with heterogeneously elevated Ca²⁺ in SR (red filled circles) mixed with jSR regions with normal or low Ca²⁺ content (black filled circles). Within contiguous regions of elevated SR Ca²⁺, aborted Ca²⁺ waves may occur but propagated waves do not normally traverse the cell. E. The same jSR Ca²⁺ load heterogeneity as in panel D but with increased sensitivity of the RyRs (See text). Under these conditions, a Ca²⁺ spark can initiate a Ca²⁺ wave.