Work

The Ca2+ transient as a feedback sensor controlling cardiomyocyte ionic conductances in mouse populations

Year: 2018

Type: article

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 computational method to predict this variability that consists of finding combinations of conductances generating a normal intracellular Ca 2+ 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 2+ and outward K + currents compensate each other to generate a normal Ca 2+ 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 2+ transient of the heart suffices to regulate ionic conductances.

Source: eLife

DOI: 10.7554/elife.36717

Authors: Colin Rees, Jun-Hai Yang, Marc Santolini, Aldons J. Lusis, James N. Weiss, Alain Karma

Institutions: Northeastern University, University of California, Los Angeles

Language: English

Topic: Cardiac electrophysiology and arrhythmias

Subfield: Cardiology and Cardiovascular Medicine

Field: Medicine

Domain: Health Sciences

Open Access status: gold

Estimated APC paid: $2,500

Funders: National Institutes of Health, National Heart, Lung, and Blood Institute