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

N1 - Funding Information:
L.T.I. was supported by National Institutes of Health/National Institute of Arthritis and Musculoskeletal and Skin Diseases Institutional Training Grant AR07592 to the Interdisciplinary Program in Muscle Biology, University of Maryland School of Medicine.

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.

UR - http://www.scopus.com/inward/record.url?scp=0035138204&partnerID=8YFLogxK

U2 - 10.1016/S0006-3495(01)75997-8

DO - 10.1016/S0006-3495(01)75997-8

M3 - Article

C2 - 11159385

AN - SCOPUS:0035138204

SN - 0006-3495

VL - 80

SP - 88

EP - 102

JO - Biophysical Journal

JF - Biophysical Journal

IS - 1

ER -