Cardiac muscle contraction is initiated by an elementary Ca signal (called Ca spark) which is achieved by collective action of Ca release channels in a cluster. The mechanism of this synchronization remains uncertain. We approached Ca spark activation as an emergent phenomenon of an interactive system of release channels. We constructed a weakly lumped Markov chain that applies an Ising model formalism to such release channel clusters and probable open channel configurations and demonstrated that spark activation is described as a system transition from a metastable to an absorbing state, analogous to the pressure required to overcome surface tension in bubble formation. This yielded quantitative estimates of the spark generation probability as a function of various system parameters. We performed numerical simulations to find spark probabilities as a function of sarcoplasmic reticulum Ca concentration, obtaining similar values for spark activation threshold as our analytic model, as well as those reported in experimental studies. Our parametric sensitivity analyses also showed that the spark activation threshold decreased as Ca sensitivity of RyR activation and RyR cluster size increased.
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28 September 2023
Research Article|
September 22 2023
Elementary intracellular Ca signals approximated as a transition of release channel system from a metastable state Available to Purchase
Special Collection:
Multiscale Modeling and Analysis in Biophysics
Guillermo Veron
;
Guillermo Veron
(Conceptualization, Data curation, Formal analysis, Investigation, Methodology, Software, Validation, Visualization, Writing – original draft, Writing – review & editing)
1
Cellular Biophysics Section, Laboratory of Cardiovascular Science, National Institute on Aging, NIH
, Baltimore, Maryland 21224, USA
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Victor A. Maltsev
;
Victor A. Maltsev
(Conceptualization, Data curation, Formal analysis, Investigation, Methodology, Project administration, Resources, Software, Supervision, Validation, Visualization, Writing – original draft, Writing – review & editing)
1
Cellular Biophysics Section, Laboratory of Cardiovascular Science, National Institute on Aging, NIH
, Baltimore, Maryland 21224, USA
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Michael D. Stern
;
Michael D. Stern
(Conceptualization, Data curation, Formal analysis, Investigation, Methodology, Software, Supervision, Validation, Visualization, Writing – review & editing)
1
Cellular Biophysics Section, Laboratory of Cardiovascular Science, National Institute on Aging, NIH
, Baltimore, Maryland 21224, USA
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Anna V. Maltsev
Anna V. Maltsev
a)
(Conceptualization, Data curation, Formal analysis, Funding acquisition, Investigation, Methodology, Project administration, Resources, Supervision, Validation, Writing – original draft, Writing – review & editing)
2
School of Mathematical Sciences, Queen Mary University of London
, London E14NS, United Kingdom
a)Author to whom correspondence should be addressed: [email protected]
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Guillermo Veron
1
Victor A. Maltsev
1
Michael D. Stern
1
Anna V. Maltsev
2,a)
1
Cellular Biophysics Section, Laboratory of Cardiovascular Science, National Institute on Aging, NIH
, Baltimore, Maryland 21224, USA
2
School of Mathematical Sciences, Queen Mary University of London
, London E14NS, United Kingdom
a)Author to whom correspondence should be addressed: [email protected]
J. Appl. Phys. 134, 124701 (2023)
Article history
Received:
March 20 2023
Accepted:
September 04 2023
Citation
Guillermo Veron, Victor A. Maltsev, Michael D. Stern, Anna V. Maltsev; Elementary intracellular Ca signals approximated as a transition of release channel system from a metastable state. J. Appl. Phys. 28 September 2023; 134 (12): 124701. https://doi.org/10.1063/5.0151255
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