Abstract
Ca(2+) blinks measure the exit of Ca(2+) from the junctional sarcoplasmic reticulum (JSR) in a cardiac myocyte during a Ca(2+) spark. Here, the relationship between experimental blink fluorescence measurements and the [Ca(2+)] in the JSR is explored using long 3D simulations of diastolic Ca(2+) release. For a fast intra-SR Ca(2+)-activated fluorophore such as Fluo-5N, we show that a simple mathematical formula relates the two for an ideal blink (i.e., when fluorescence signals come only from the JSR). The formula shows that normalized JSR [Ca(2+)] is much lower than the normalized fluorescence and that JSR Ca(2+) depletes ∼40-50% more than previously inferred from blink fluorescence measurements. In addition, we show that stray fluorescence signals (e.g., from other parts of the sarcoplasmic reticulum network) can mask even deeper Ca(2+) depletion. Overall, the simulations show that strong JSR Ca(2+) depletion such as that seen in many simulations is consistent with the relatively moderate fluorescence changes seen in experiments.