Large currents generate cardiac Ca2+ sparks

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

Research output: Contribution to journalArticle

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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 (US)
Pages (from-to)88-102
Number of pages15
JournalBiophysical Journal
Volume80
Issue number1
StatePublished - 2001
Externally publishedYes

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Buffers
Theoretical Models
Coloring Agents
Fluorescence
Proteins
Pseudechis venom

ASJC Scopus subject areas

  • Biophysics

Cite this

Izu, L. T., Mauban, J. R. H., Balke, C. W., & Wier, W. G. (2001). Large currents generate cardiac Ca2+ sparks. Biophysical Journal, 80(1), 88-102.

Large currents generate cardiac Ca2+ sparks. / Izu, Leighton T; Mauban, Joseph R H; Balke, C. W.; Wier, W. Gil.

In: Biophysical Journal, Vol. 80, No. 1, 2001, p. 88-102.

Research output: Contribution to journalArticle

Izu, LT, Mauban, JRH, Balke, CW & Wier, WG 2001, 'Large currents generate cardiac Ca2+ sparks', Biophysical Journal, vol. 80, no. 1, pp. 88-102.
Izu LT, Mauban JRH, Balke CW, Wier WG. Large currents generate cardiac Ca2+ sparks. Biophysical Journal. 2001;80(1):88-102.
Izu, Leighton T ; Mauban, Joseph R H ; Balke, C. W. ; Wier, W. Gil. / Large currents generate cardiac Ca2+ sparks. In: Biophysical Journal. 2001 ; Vol. 80, No. 1. pp. 88-102.
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