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The Ca 2+ transient as a feedback sensor controlling cardiomyocyte ionic conductances in mouse populations.
- Source :
-
ELife [Elife] 2018 Sep 25; Vol. 7. Date of Electronic Publication: 2018 Sep 25. - Publication Year :
- 2018
-
Abstract
- Conductances of ion channels and transporters controlling cardiac excitation may vary in a population of subjects with different cardiac gene expression patterns. However, the amount of variability and its origin are not quantitatively known. We propose a new conceptual approach to predict this variability that consists of finding combinations of conductances generating a normal intracellular Ca <superscript>2+</superscript> transient without any constraint on the action potential. Furthermore, we validate experimentally its predictions using the Hybrid Mouse Diversity Panel, a model system of genetically diverse mouse strains that allows us to quantify inter-subject versus intra-subject variability. The method predicts that conductances of inward Ca <superscript>2+</superscript> and outward K <superscript>+</superscript> currents compensate each other to generate a normal Ca <superscript>2+</superscript> transient in good quantitative agreement with current measurements in ventricular myocytes from hearts of different isogenic strains. Our results suggest that a feedback mechanism sensing the aggregate Ca <superscript>2+</superscript> transient of the heart suffices to regulate ionic conductances.<br />Competing Interests: CR, JY, MS, AL, JW, AK No competing interests declared<br /> (© 2018, Rees et al.)
Details
- Language :
- English
- ISSN :
- 2050-084X
- Volume :
- 7
- Database :
- MEDLINE
- Journal :
- ELife
- Publication Type :
- Academic Journal
- Accession number :
- 30251624
- Full Text :
- https://doi.org/10.7554/eLife.36717