### Abstract

Previous models of cardiac Ca^{2+} sparks have assumed that Ca^{2+} currents through the Ca^{2+} release units (CRUs) were ∼1-2 pA, producing sparks with peak fluorescence ratio (F/F_{o}) of ∼2.0 and a full-width at half maximum (FWHM) of ∼1 μm. Here, we present actual Ca^{2+} sparks with peak F/F_{o} 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 Ca^{2+} current. Assuming infinite reaction rates and no endogenous buffers, we obtain a lower bound of ∼11 pA needed to generate a Ca^{2+} spark with FWHM of 2 μm. Under realistic conditions, the CRU current must be ∼20 pA to generate a 2-μm Ca^{2+} spark. For currents ≥5 pA, the computed spark amplitudes (F/F_{o}) 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 Ca^{2+} "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 Ca^{2+} sparks are significantly larger in peak amplitude than previously thought, that such large Ca^{2+} sparks are consistent with the measured FWHM of ∼2 μm, and that the underlying Ca^{2+} current is in the range of 10-20 pA.

Original language | English (US) |
---|---|

Pages (from-to) | 88-102 |

Number of pages | 15 |

Journal | Biophysical Journal |

Volume | 80 |

Issue number | 1 |

State | Published - 2001 |

Externally published | Yes |

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### ASJC Scopus subject areas

- Biophysics

### Cite this

^{2+}sparks.

*Biophysical Journal*,

*80*(1), 88-102.

**Large currents generate cardiac Ca ^{2+} sparks.** / Izu, Leighton T; Mauban, Joseph R H; Balke, C. W.; Wier, W. Gil.

Research output: Contribution to journal › Article

^{2+}sparks',

*Biophysical Journal*, vol. 80, no. 1, pp. 88-102.

^{2+}sparks. Biophysical Journal. 2001;80(1):88-102.

}

TY - JOUR

T1 - Large currents generate cardiac Ca2+ sparks

AU - Izu, Leighton T

AU - Mauban, Joseph R H

AU - Balke, C. W.

AU - Wier, W. Gil

PY - 2001

Y1 - 2001

N2 - 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.

AB - 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.

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M3 - Article

VL - 80

SP - 88

EP - 102

JO - Biophysical Journal

JF - Biophysical Journal

SN - 0006-3495

IS - 1

ER -