Authors J. Koivumäki, R. Clark, D. Belke, C. Kondo, P. Fedak, M. Maleckar and W. R. Giles Title Na+ Current Expression in Human Atrial Myofibroblasts: Its Identity and Functional Consequences Afilliation Scientific Computing, , Scientific Computing Project(s) Center for Biomedical Computing (SFF) Status Published Publication Type Journal Article Year of Publication 2014 Journal Frontiers in Physiology Volume 5 Number 5 Pagination 275 Date Published August Publisher Abstract 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 Key Simula.simula.2492