The role of intracellular Ca buffers in determining the shape of the systolic Ca transient in cardiac ventricular myocytes

Abstract

We have studied the kinetics of decay of cardiac Ca transients elicited by either caffeine or electrical stimulation. The decay of the caffeine-evoked increase of intracellular Ca concentration ([Ca2+]i) could not be fit by a single exponential. A two exponential fit showed an initial rapid component. The rate of decay of total Ca was calculated from measured free Ca and the buffering properties of the cell. There was no initial rapid phase of decay of total Ca. We conclude that the rapid phase of decay of free Ca is due to a decrease of Ca buffering power at elevated [Ca2+]i. In contrast, the decay of the Ca transient, produced by voltage-clamp depolarization or field stimulation was fit by a single exponential. We suggest that these apparently simple kinetics arise because a tendency to saturation at elevated [Ca2+]i of the sarcoplasmic reticulum Ca-ATPase offsets the decrease of Ca buffering power. These data show the importance of Ca buffers as well as transporters in determining the kinetics of changes of [Ca2+]i.

Modest Reductions of Cardiac Calsequestrin Increase Sarcoplasmic Reticulum Ca 2+ Leak Independent of Luminal Ca 2+ and Trigger Ventricular Arrhythmias in Mice

“…Another limitation is that we used the tetracaineinduced drop in diastolic Fura-2 fluorescent ratio as an estimate of diastolic SR Ca 2ϩ leak ( Figure 7A). Given the nonlinear relationship between Ca 2ϩ and fluorescence ratio and the nonlinear buffering properties of the cytoplasm, 26 our results cannot be directly compared with Ca 2ϩ leak rates obtain in other studies. 16,27 The finding that even a modest decrease in Casq2 increases arrhythmia susceptibility has potential clinical implications.…”

Excess of glucocorticoid induces myocardial remodeling and alteration of calcium signaling in cardiomyocytes

“…An increased Ca 2C -buffering capacity of the SR lumen leading to lower intraluminal free Ca 2C concentrations and hence lower amount of Ca 2C is released. It is well known that Ca 2C removal from the cytosol after a caffeine response is largely dependent on the activity of Na C /Ca 2C exchanger (Díaz et al 2001). In DEX-treated heart, the expression of Na C /Ca 2C exchanger is increased (Fig.…”

Comparable calcium handling of human iPSC-derived cardiomyocytes generated by multiple laboratories

“…3). The latter result is of critical importance for interpreting results from experiments using fluorescent Ca indicators in CMs [33], an approach that is widely used for measuring Ca transients and SR Ca content. Finally, our results demonstrate that independently generated hiPSC-CM lines from healthy donors exhibit comparable and reproducible Ca handling and cytosolic Ca buffering properties.…”