Large currents generate cardiac Ca2+ sparks

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

Research output: Contribution to journalArticle

68 Scopus citations

Abstract

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/Fo) of ∼2.0 and a full-width at half maximum (FWHM) of ∼1 μm. Here, we present actual Ca2+ sparks with peak F/Fo 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/Fo) 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.

Original languageEnglish
Pages (from-to)88-102
Number of pages15
JournalBiophysical Journal
Volume80
Issue number1
DOIs
StatePublished - Jan 1 2001
Externally publishedYes

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