Fig. 6.

Regenerative CICR facilitates propagation of the Ca²⁺ signal from the plasmalemma to the center of the soma and into the nucleus. A, C, Calcium green-1-based confocal images show the distribution of [Ca²⁺] during electrical stimulation for the same cell in the absence (A) and presence (C) of 5 mm caffeine. Fluorescent intensity was normalized to that at rest (F/F₀) and used as an index of [Ca²⁺]. The horizontal color bar indicates relative fluorescence intensity. Elevations in [Ca²⁺] were elicited by extracellular field stimulation applied at 5 Hz for 0.9 sec (A) or 0.4 sec (C). The stimulus strength was adjusted to produce comparable peak [Ca²⁺] levels. Times at which the images were captured are indicated under the corresponding images. The resting images were taken immediately before stimulation. B, D, The time course of the changes in [Ca²⁺] is plotted in the absence (B) and presence (D) of 5 mm caffeine. [Ca²⁺] was measured at the rim (red), center (green), and nucleus (black) of the cell as shown inE. The duration of the stimulus is indicatedunder each plot. The vertical arrowsindicate the times at which the images presented in Aand C were captured. E, Raw calcium green-1 fluorescence for the cell described in A–D.Rectangles indicate areas for which changes in [Ca²⁺]_i are plotted inB and D. The intensity of fluorescence in a resting cell is much higher in the nucleus (O’Malley, 1994), enabling its unambiguous identification. F, Changes in [Ca²⁺] in the center of the soma and in the nucleus are compared with those at the rim when CICR was (open bar) and was not (solid bar) recruited (n = 6). *p < 0.05; **p < 0.01; paired Student’s ttest.