AuthorsJ. Koivumäki, R. Clark, D. Belke, C. Kondo, P. Fedak, M. Maleckar and W. R. Giles
TitleNa+ Current Expression in Human Atrial Myofibroblasts: Its Identity and Functional Consequences
AfilliationScientific Computing, , Scientific Computing
Project(s)Center for Biomedical Computing (SFF)
Publication TypeJournal Article
Year of Publication2014
JournalFrontiers in Physiology
Date PublishedAugust

In the mammalian heart fibroblasts have important functions in both healthy and diseased states. During pathophysiological challenges, a closely related myofibroblast cell population can play distinct and significant roles. Recently, it has been reported that human atrial myofibroblasts can express a Na+ current, INa. Some of the biophysical properties and molecular features of the corresponding integral membrane protein suggest that this INa is due to expression of Nav 1.5. This is the same Na+ channel \alpha subunit that generates the predominant INa in myocytes from adult mammalian heart. In principle, expression of Nav 1.5 could give rise to regenerative action potentials in the fibroblasts/myofibroblasts. If so, this would suggest an active as opposed to passive role for fibroblasts/myofibroblasts in both the {`}trigger' and the {`}substrate' components of cardiac rhythm disturbances. Our goals were: (i) to confirm and extend the electrophysiological and biophysical characterization of INa in a human atrial fibroblast/myofibroblast cell population maintained in tissue culture; (ii) to identify the molecular features of the \alpha and \beta subunits of the Na+ channel(s) that are expressed in these myofibroblasts; (iii) to define the biophysical and pharmacological properties of this Na+ current; (iv) to integrate the available multi-disciplinary data, and illustrate its functional consequences, using a mathematical model in which the human atrial myocyte is coupled to fibroblasts/myofibroblasts in a syncytial structure. Our experimental findings confirm that a significant fraction (\~50%) of human atrial myofibroblasts express INa and address the previous finding that Nav 1.5 is the predominant Na+ channel \alpha subunit isoform. These electrophysiological and molecular findings, when complemented with our mathematical modeling, provide a basis for re-evaluating pharmacological approaches for the management of supraventricular rhythm disorders, e.g. persistent atrial fibrillation.

Citation KeySimula.simula.2492