TY - JOUR

T1 - A four-compartment model for Ca2+ dynamics

T2 - An interpretation of Ca2+ decay after repetitive firing of intact nerve terminals

AU - Peng, Yan Yi

AU - Wang, Kwang Shang

N1 - Funding Information:
The Fortran program was a kind gift from Dr. Dorothy A. Hanck. It was called by a program written in IGOR (Wavemetrics). The rest of the analysis was carried out by use of IGOR routines that were developed in collaboration with Mr. Chi Chueng. We thank Drs. John Milton and Phillip Ulinski for their critiques of the manuscript and Ms. Elisabeth Lanzl for editing the manuscript. This work was supported by an Alfred P. Sloan fellowship, NIH grant NS32429, and a grant from the Brain Research Foundation to Y.-Y. Peng.

PY - 2000

Y1 - 2000

N2 - In the presynaptic nerve terminals of the bullfrog sympathetic ganglia, repetitive nerve firing evokes [Ca2+] transients that decay monotonically. An algorithm based on an eigenfunction expansion method was used for fitting these [Ca2+] decay records. The data were fitted by a linear combination of two to four exponential functions. A mathematical model with three intraterminal membrane-bound compartments was developed to describe the observed Ca2+ decay. The model predicts that the number of exponential functions, n, contained in the decay data corresponds to n - 1 intraterminal Ca2+ stores that release Ca2+ during the decay. Moreover, when a store stops releasing or starts to release Ca2+, the decay data should be fitted by functions that contain one less exponential component for the former and one more for the latter than do the fitting functions for control data. Because of the current lack of a parameter by which quantitative comparisons can be made between two decay processes when at least one of them contained more than one exponential components, we defined a parameter, the overall rate (OR) of decay, as the trace of the coefficient matrix of the differential equation systems of our model. We used the mathematical properties of the model and of the OR to interpret effects of ryanodine and of a mitochondria uncoupler on Ca2+ decay. The results of the analysis were consistent with the ryanodine-sensitive store, mitochondria, and another, yet unidentified store release Ca2+ into the cytosol of the presynaptic nerve terminals during Ca2+ decay. Our model also predicts that mitochondrial Ca2+ buffering accounted for more than 86% of all the flux rates across various membranes combined and that there are type 3 and type 1 and/or type 2 ryanodine receptors in these terminals.

AB - In the presynaptic nerve terminals of the bullfrog sympathetic ganglia, repetitive nerve firing evokes [Ca2+] transients that decay monotonically. An algorithm based on an eigenfunction expansion method was used for fitting these [Ca2+] decay records. The data were fitted by a linear combination of two to four exponential functions. A mathematical model with three intraterminal membrane-bound compartments was developed to describe the observed Ca2+ decay. The model predicts that the number of exponential functions, n, contained in the decay data corresponds to n - 1 intraterminal Ca2+ stores that release Ca2+ during the decay. Moreover, when a store stops releasing or starts to release Ca2+, the decay data should be fitted by functions that contain one less exponential component for the former and one more for the latter than do the fitting functions for control data. Because of the current lack of a parameter by which quantitative comparisons can be made between two decay processes when at least one of them contained more than one exponential components, we defined a parameter, the overall rate (OR) of decay, as the trace of the coefficient matrix of the differential equation systems of our model. We used the mathematical properties of the model and of the OR to interpret effects of ryanodine and of a mitochondria uncoupler on Ca2+ decay. The results of the analysis were consistent with the ryanodine-sensitive store, mitochondria, and another, yet unidentified store release Ca2+ into the cytosol of the presynaptic nerve terminals during Ca2+ decay. Our model also predicts that mitochondrial Ca2+ buffering accounted for more than 86% of all the flux rates across various membranes combined and that there are type 3 and type 1 and/or type 2 ryanodine receptors in these terminals.

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U2 - 10.1023/A:1008954127682

DO - 10.1023/A:1008954127682

M3 - Article

C2 - 10809016

AN - SCOPUS:0033625462

VL - 8

SP - 275

EP - 298

JO - Journal of Computational Neuroscience

JF - Journal of Computational Neuroscience

SN - 0929-5313

IS - 3

ER -