Biophys J, January 2001, p. 88-102, Vol. 80, No. 1

Large Currents Generate Cardiac Ca²⁺ Sparks

Leighton T. Izu,^* Joseph R. H. Mauban, C. W. Balke,^* and W. Gil Wier^*

Departments of  ^*Medicine and  Physiology, University of Maryland, Baltimore, Baltimore, Maryland 21201, USA

Previous models of cardiac Ca²⁺ sparks have assumed that Ca²⁺ currents through the Ca²⁺ release units (CRUs) were ~1-2 pA, producing sparks with peak fluorescence ratio (F/F₀) of ~2.0 and a full-width at half maximum (FWHM) of ~1 µm. Here, we present actual Ca²⁺ sparks with peak F/F₀ of >6 and a FWHM of ~2 µm, and a mathematical model of such sparks, the main feature of which is a much larger underlying Ca²⁺ current. Assuming infinite reaction rates and no endogenous buffers, we obtain a lower bound of ~11 pA needed to generate a Ca²⁺ spark with FWHM of 2 µm. Under realistic conditions, the CRU current must be ~20 pA to generate a 2-µm Ca²⁺ spark. For currents 5 pA, the computed spark amplitudes (F/F₀) are large (~6-12 depending on buffer model). We considered several factors that might produce sparks with FWHM ~ 2 µm without using large currents. Possible protein-dye interactions increased the FWHM slightly. Hypothetical Ca²⁺ "quarks" had little effect, as did blurring of sparks by the confocal microscope. A clusters of CRUs, each producing 10 pA simultaneously, can produce sparks with FWHM ~ 2 µm. We conclude that cardiac Ca²⁺ sparks are significantly larger in peak amplitude than previously thought, that such large Ca²⁺ sparks are consistent with the measured FWHM of ~2 µm, and that the underlying Ca²⁺ current is in the range of 10-20 pA.

Biophys J, January 2001, p. 88-102, Vol. 80, No. 1
© 2001 by the Biophysical Society   0006-3495/01/01/88/15  $2.00

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