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Variable setpoint as a relaxing component in physiological control

Setpoints in physiology have been a puzzle for decades, and especially the notion of fixed or variable setpoints have received much attention. In this paper, we show how previously presented homeostatic controller motifs, extended with saturable signaling kinetics, can be described as variable setpo...

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Autores principales: Risvoll, Geir B., Thorsen, Kristian, Ruoff, Peter, Drengstig, Tormod
Formato: Online Artículo Texto
Lenguaje:English
Publicado: John Wiley and Sons Inc. 2017
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5599866/
https://www.ncbi.nlm.nih.gov/pubmed/28904081
http://dx.doi.org/10.14814/phy2.13408
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author Risvoll, Geir B.
Thorsen, Kristian
Ruoff, Peter
Drengstig, Tormod
author_facet Risvoll, Geir B.
Thorsen, Kristian
Ruoff, Peter
Drengstig, Tormod
author_sort Risvoll, Geir B.
collection PubMed
description Setpoints in physiology have been a puzzle for decades, and especially the notion of fixed or variable setpoints have received much attention. In this paper, we show how previously presented homeostatic controller motifs, extended with saturable signaling kinetics, can be described as variable setpoint controllers. The benefit of a variable setpoint controller is that an observed change in the concentration of the regulated biochemical species (the controlled variable) is fully characterized, and is not considered a deviation from a fixed setpoint. The variation in this biochemical species originate from variation in the disturbances (the perturbation), and thereby in the biochemical species representing the controller (the manipulated variable). Thus, we define an operational space which is spanned out by the combined high and low levels of the variations in (1) the controlled variable, (2) the manipulated variable, and (3) the perturbation. From this operational space, we investigate whether and how it imposes constraints on the different motif parameters, in order for the motif to represent a mathematical model of the regulatory system. Further analysis of the controller's ability to compensate for disturbances reveals that a variable setpoint represents a relaxing component for the controller, in that the necessary control action is reduced compared to that of a fixed setpoint controller. Such a relaxing component might serve as an important property from an evolutionary point of view. Finally, we illustrate the principles using the renal sodium and aldosterone regulatory system, where we model the variation in plasma sodium as a function of salt intake. We show that the experimentally observed variations in plasma sodium can be interpreted as a variable setpoint regulatory system.
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spelling pubmed-55998662017-09-19 Variable setpoint as a relaxing component in physiological control Risvoll, Geir B. Thorsen, Kristian Ruoff, Peter Drengstig, Tormod Physiol Rep Original Research Setpoints in physiology have been a puzzle for decades, and especially the notion of fixed or variable setpoints have received much attention. In this paper, we show how previously presented homeostatic controller motifs, extended with saturable signaling kinetics, can be described as variable setpoint controllers. The benefit of a variable setpoint controller is that an observed change in the concentration of the regulated biochemical species (the controlled variable) is fully characterized, and is not considered a deviation from a fixed setpoint. The variation in this biochemical species originate from variation in the disturbances (the perturbation), and thereby in the biochemical species representing the controller (the manipulated variable). Thus, we define an operational space which is spanned out by the combined high and low levels of the variations in (1) the controlled variable, (2) the manipulated variable, and (3) the perturbation. From this operational space, we investigate whether and how it imposes constraints on the different motif parameters, in order for the motif to represent a mathematical model of the regulatory system. Further analysis of the controller's ability to compensate for disturbances reveals that a variable setpoint represents a relaxing component for the controller, in that the necessary control action is reduced compared to that of a fixed setpoint controller. Such a relaxing component might serve as an important property from an evolutionary point of view. Finally, we illustrate the principles using the renal sodium and aldosterone regulatory system, where we model the variation in plasma sodium as a function of salt intake. We show that the experimentally observed variations in plasma sodium can be interpreted as a variable setpoint regulatory system. John Wiley and Sons Inc. 2017-09-14 /pmc/articles/PMC5599866/ /pubmed/28904081 http://dx.doi.org/10.14814/phy2.13408 Text en © 2017 The Authors. Physiological Reports published by Wiley Periodicals, Inc. on behalf of The Physiological Society and the American Physiological Society This is an open access article under the terms of the Creative Commons Attribution (http://creativecommons.org/licenses/by/4.0/) License, which permits use, distribution and reproduction in any medium, provided the original work is properly cited.
spellingShingle Original Research
Risvoll, Geir B.
Thorsen, Kristian
Ruoff, Peter
Drengstig, Tormod
Variable setpoint as a relaxing component in physiological control
title Variable setpoint as a relaxing component in physiological control
title_full Variable setpoint as a relaxing component in physiological control
title_fullStr Variable setpoint as a relaxing component in physiological control
title_full_unstemmed Variable setpoint as a relaxing component in physiological control
title_short Variable setpoint as a relaxing component in physiological control
title_sort variable setpoint as a relaxing component in physiological control
topic Original Research
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5599866/
https://www.ncbi.nlm.nih.gov/pubmed/28904081
http://dx.doi.org/10.14814/phy2.13408
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