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Calcium-dependent inactivation terminates calcium release in skeletal muscle of amphibians.

Ríos E, Zhou J, Brum G, Launikonis BS, Stern MD - J. Gen. Physiol. (2008)

Bottom Line: In groups of thousands of sparks occurring spontaneously in membrane-permeabilized frog muscle cells a complex relationship was found between amplitude a and rise time T, which in sparks corresponds to the active time of the underlying Ca2+ release.Using every method, it was found that T and flux were inversely correlated, roughly inversely proportional.Considering these results and other available evidence it is concluded that Ca2+-dependent inactivation, or CDI, provides the crucial mechanism for termination of sparks and cell-wide Ca2+ release in amphibians.

View Article: PubMed Central - PubMed

Affiliation: Section of Cellular Signaling, Department of Molecular Biophysics and Physiology, Rush University, Chicago, IL 60612, USA.

ABSTRACT
In skeletal muscle of amphibians, the cell-wide cytosolic release of calcium that enables contraction in response to an action potential appears to be built of Ca2+ sparks. The mechanism that rapidly terminates this release was investigated by studying the termination of Ca2+ release underlying sparks. In groups of thousands of sparks occurring spontaneously in membrane-permeabilized frog muscle cells a complex relationship was found between amplitude a and rise time T, which in sparks corresponds to the active time of the underlying Ca2+ release. This relationship included a range of T where a paradoxically decreased with increasing T. Three different methods were used to estimate Ca2+ release flux in groups of sparks of different T. Using every method, it was found that T and flux were inversely correlated, roughly inversely proportional. A simple model in which release sources were inactivated by cytosolic Ca2+ was able to explain the relationship. The predictive value of the model, evaluated by analyzing the variance of spark amplitude, was found to be high when allowance was made for the out-of-focus error contribution to the total variance. This contribution was estimated using a theory of confocal scanning (Ríos, E., N. Shirokova, W.G. Kirsch, G. Pizarro, M.D. Stern, H. Cheng, and A. González. Biophys. J. 2001. 80:169-183), which was confirmed in the present work by simulated line scanning of simulated sparks. Considering these results and other available evidence it is concluded that Ca2+-dependent inactivation, or CDI, provides the crucial mechanism for termination of sparks and cell-wide Ca2+ release in amphibians. Given the similarities in kinetics of release termination observed in cell-averaged records of amphibian and mammalian muscle, and in spite of differences in activation mechanisms, CDI is likely to play a central role in mammals as well. Trivially, an inverse proportionality between release flux and duration, in sparks or in global release of skeletal muscle, maintains constancy of the amount of released Ca2+.

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Recovery of “true amplitudes” from distributions of scanned amplitudes. (A) Histograms f(as) of scanned amplitudes for a set of sparks consisting in three groups with equal numbers, simulated using three values of current (5, 20, and 50 pA) at three durations (5, 10, and 20 ms). Three alternative binning intervals were used, as indicated. The distribution of true amplitudes in the simulation consists therefore of three Dirac deltas (see below). (B) Distributions g(a) of true amplitudes, derived from f(as) in A using Eq. A1. Dashed lines mark the position of true (in-focus) amplitudes of simulated sparks, 0.634, 2.27, and 3.66. Narrow binning is best at locating low amplitude modes and vice versa.
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fig8: Recovery of “true amplitudes” from distributions of scanned amplitudes. (A) Histograms f(as) of scanned amplitudes for a set of sparks consisting in three groups with equal numbers, simulated using three values of current (5, 20, and 50 pA) at three durations (5, 10, and 20 ms). Three alternative binning intervals were used, as indicated. The distribution of true amplitudes in the simulation consists therefore of three Dirac deltas (see below). (B) Distributions g(a) of true amplitudes, derived from f(as) in A using Eq. A1. Dashed lines mark the position of true (in-focus) amplitudes of simulated sparks, 0.634, 2.27, and 3.66. Narrow binning is best at locating low amplitude modes and vice versa.

Mentions: The simulations done to test the theory of line scanning are described in the Appendix. To examine the pure effect of scan line offset on the distribution of apparent spark amplitudes, a population of sparks with random offsets from the scanned line, but fixed source current and duration, was generated. This study is illustrated with Fig. A1. To test the ability of theory to recover the “true amplitude” distribution of a set of sparks from the distribution of amplitudes measured in line scans, a large set of simulated sparks was generated with three different values of release current and release duration. The results of these are presented in Figs. A2 and A3.


Calcium-dependent inactivation terminates calcium release in skeletal muscle of amphibians.

Ríos E, Zhou J, Brum G, Launikonis BS, Stern MD - J. Gen. Physiol. (2008)

Recovery of “true amplitudes” from distributions of scanned amplitudes. (A) Histograms f(as) of scanned amplitudes for a set of sparks consisting in three groups with equal numbers, simulated using three values of current (5, 20, and 50 pA) at three durations (5, 10, and 20 ms). Three alternative binning intervals were used, as indicated. The distribution of true amplitudes in the simulation consists therefore of three Dirac deltas (see below). (B) Distributions g(a) of true amplitudes, derived from f(as) in A using Eq. A1. Dashed lines mark the position of true (in-focus) amplitudes of simulated sparks, 0.634, 2.27, and 3.66. Narrow binning is best at locating low amplitude modes and vice versa.
© Copyright Policy
Related In: Results  -  Collection

Show All Figures
getmorefigures.php?uid=PMC2279174&req=5

fig8: Recovery of “true amplitudes” from distributions of scanned amplitudes. (A) Histograms f(as) of scanned amplitudes for a set of sparks consisting in three groups with equal numbers, simulated using three values of current (5, 20, and 50 pA) at three durations (5, 10, and 20 ms). Three alternative binning intervals were used, as indicated. The distribution of true amplitudes in the simulation consists therefore of three Dirac deltas (see below). (B) Distributions g(a) of true amplitudes, derived from f(as) in A using Eq. A1. Dashed lines mark the position of true (in-focus) amplitudes of simulated sparks, 0.634, 2.27, and 3.66. Narrow binning is best at locating low amplitude modes and vice versa.
Mentions: The simulations done to test the theory of line scanning are described in the Appendix. To examine the pure effect of scan line offset on the distribution of apparent spark amplitudes, a population of sparks with random offsets from the scanned line, but fixed source current and duration, was generated. This study is illustrated with Fig. A1. To test the ability of theory to recover the “true amplitude” distribution of a set of sparks from the distribution of amplitudes measured in line scans, a large set of simulated sparks was generated with three different values of release current and release duration. The results of these are presented in Figs. A2 and A3.

Bottom Line: In groups of thousands of sparks occurring spontaneously in membrane-permeabilized frog muscle cells a complex relationship was found between amplitude a and rise time T, which in sparks corresponds to the active time of the underlying Ca2+ release.Using every method, it was found that T and flux were inversely correlated, roughly inversely proportional.Considering these results and other available evidence it is concluded that Ca2+-dependent inactivation, or CDI, provides the crucial mechanism for termination of sparks and cell-wide Ca2+ release in amphibians.

View Article: PubMed Central - PubMed

Affiliation: Section of Cellular Signaling, Department of Molecular Biophysics and Physiology, Rush University, Chicago, IL 60612, USA.

ABSTRACT
In skeletal muscle of amphibians, the cell-wide cytosolic release of calcium that enables contraction in response to an action potential appears to be built of Ca2+ sparks. The mechanism that rapidly terminates this release was investigated by studying the termination of Ca2+ release underlying sparks. In groups of thousands of sparks occurring spontaneously in membrane-permeabilized frog muscle cells a complex relationship was found between amplitude a and rise time T, which in sparks corresponds to the active time of the underlying Ca2+ release. This relationship included a range of T where a paradoxically decreased with increasing T. Three different methods were used to estimate Ca2+ release flux in groups of sparks of different T. Using every method, it was found that T and flux were inversely correlated, roughly inversely proportional. A simple model in which release sources were inactivated by cytosolic Ca2+ was able to explain the relationship. The predictive value of the model, evaluated by analyzing the variance of spark amplitude, was found to be high when allowance was made for the out-of-focus error contribution to the total variance. This contribution was estimated using a theory of confocal scanning (Ríos, E., N. Shirokova, W.G. Kirsch, G. Pizarro, M.D. Stern, H. Cheng, and A. González. Biophys. J. 2001. 80:169-183), which was confirmed in the present work by simulated line scanning of simulated sparks. Considering these results and other available evidence it is concluded that Ca2+-dependent inactivation, or CDI, provides the crucial mechanism for termination of sparks and cell-wide Ca2+ release in amphibians. Given the similarities in kinetics of release termination observed in cell-averaged records of amphibian and mammalian muscle, and in spite of differences in activation mechanisms, CDI is likely to play a central role in mammals as well. Trivially, an inverse proportionality between release flux and duration, in sparks or in global release of skeletal muscle, maintains constancy of the amount of released Ca2+.

Show MeSH
Related in: MedlinePlus