A large population of cell-specific action potential models replicating fluorescence recordings of voltage in rabbit ventricular myocytes
Recent high-throughput experiments unveil substantial electrophysiological diversity among uncoupled healthy myocytes under identical conditions. To quantify inter-cell variability, the values of a subset of the parameters in a well-regarded mathematical model of the action potential of rabbit ventr...
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| Language: | English |
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The Royal Society
2025-03-01
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| Series: | Royal Society Open Science |
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| Online Access: | https://royalsocietypublishing.org/doi/10.1098/rsos.241539 |
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| author | Radostin D. Simitev Rebecca J. Gilchrist Zhechao Yang Rachel C. Myles Francis L. Burton Godfrey L. Smith |
| author_facet | Radostin D. Simitev Rebecca J. Gilchrist Zhechao Yang Rachel C. Myles Francis L. Burton Godfrey L. Smith |
| author_sort | Radostin D. Simitev |
| collection | DOAJ |
| description | Recent high-throughput experiments unveil substantial electrophysiological diversity among uncoupled healthy myocytes under identical conditions. To quantify inter-cell variability, the values of a subset of the parameters in a well-regarded mathematical model of the action potential of rabbit ventricular myocytes are estimated from fluorescence voltage measurements of a large number of cells. Statistical inference yields a population of nearly 1200 cell-specific model variants that, on a population-level replicate experimentally measured biomarker ranges and distributions, and in contrast to earlier studies, also match experimental biomarker values on a cell-by-cell basis. This model population may be regarded as a random sample from the phenotype of healthy rabbit ventricular myocytes. Univariate and bivariate joint marginal distributions of the estimated parameters are presented, and the parameter dependencies of several commonly used electrophysiological biomarkers are determined. Parameter values are weakly correlated, while summary metrics such as the action potential duration are not strongly dependent on any single electrophysiological characteristic of the myocyte. Our results demonstrate the feasibility of accurately and efficiently fitting entire action potential waveforms at scale. |
| format | Article |
| id | doaj-art-a26a5d7bee4144ce90813270da055bb9 |
| institution | DOAJ |
| issn | 2054-5703 |
| language | English |
| publishDate | 2025-03-01 |
| publisher | The Royal Society |
| record_format | Article |
| series | Royal Society Open Science |
| spelling | doaj-art-a26a5d7bee4144ce90813270da055bb92025-08-20T02:42:14ZengThe Royal SocietyRoyal Society Open Science2054-57032025-03-0112310.1098/rsos.241539A large population of cell-specific action potential models replicating fluorescence recordings of voltage in rabbit ventricular myocytesRadostin D. Simitev0Rebecca J. Gilchrist1Zhechao Yang2Rachel C. Myles3Francis L. Burton4Godfrey L. Smith5School of Mathematics and Statistics, University of Glasgow, Glasgow, UKSchool of Cardiovascular and Metabolic Health, University of Glasgow, Glasgow, UKSchool of Mathematics and Statistics, University of Glasgow, Glasgow, UKSchool of Cardiovascular and Metabolic Health, University of Glasgow, Glasgow, UKSchool of Cardiovascular and Metabolic Health, University of Glasgow, Glasgow, UKSchool of Cardiovascular and Metabolic Health, University of Glasgow, Glasgow, UKRecent high-throughput experiments unveil substantial electrophysiological diversity among uncoupled healthy myocytes under identical conditions. To quantify inter-cell variability, the values of a subset of the parameters in a well-regarded mathematical model of the action potential of rabbit ventricular myocytes are estimated from fluorescence voltage measurements of a large number of cells. Statistical inference yields a population of nearly 1200 cell-specific model variants that, on a population-level replicate experimentally measured biomarker ranges and distributions, and in contrast to earlier studies, also match experimental biomarker values on a cell-by-cell basis. This model population may be regarded as a random sample from the phenotype of healthy rabbit ventricular myocytes. Univariate and bivariate joint marginal distributions of the estimated parameters are presented, and the parameter dependencies of several commonly used electrophysiological biomarkers are determined. Parameter values are weakly correlated, while summary metrics such as the action potential duration are not strongly dependent on any single electrophysiological characteristic of the myocyte. Our results demonstrate the feasibility of accurately and efficiently fitting entire action potential waveforms at scale.https://royalsocietypublishing.org/doi/10.1098/rsos.241539cellular excitabilityrabbit ventricular myocytesfluorescence voltage measurementsaction potential waveformparameter estimation in differential equationsnoisy time series |
| spellingShingle | Radostin D. Simitev Rebecca J. Gilchrist Zhechao Yang Rachel C. Myles Francis L. Burton Godfrey L. Smith A large population of cell-specific action potential models replicating fluorescence recordings of voltage in rabbit ventricular myocytes Royal Society Open Science cellular excitability rabbit ventricular myocytes fluorescence voltage measurements action potential waveform parameter estimation in differential equations noisy time series |
| title | A large population of cell-specific action potential models replicating fluorescence recordings of voltage in rabbit ventricular myocytes |
| title_full | A large population of cell-specific action potential models replicating fluorescence recordings of voltage in rabbit ventricular myocytes |
| title_fullStr | A large population of cell-specific action potential models replicating fluorescence recordings of voltage in rabbit ventricular myocytes |
| title_full_unstemmed | A large population of cell-specific action potential models replicating fluorescence recordings of voltage in rabbit ventricular myocytes |
| title_short | A large population of cell-specific action potential models replicating fluorescence recordings of voltage in rabbit ventricular myocytes |
| title_sort | large population of cell specific action potential models replicating fluorescence recordings of voltage in rabbit ventricular myocytes |
| topic | cellular excitability rabbit ventricular myocytes fluorescence voltage measurements action potential waveform parameter estimation in differential equations noisy time series |
| url | https://royalsocietypublishing.org/doi/10.1098/rsos.241539 |
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