|Authors||M. Frisk, J. Koivumäki, P. A. Norseng, M. Maleckar, O. M. Sejersted and W. E. Louch|
|Title||Variable T-Tubule Organization and Ca2+ Homeostasis Across the Atria|
|Afilliation||Scientific Computing, , Scientific Computing|
|Project(s)||Center for Biomedical Computing (SFF)|
|Publication Type||Journal Article|
|Year of Publication||2014|
|Journal||Heart and Circulatory Physiology|
Rationale: Although t-tubules have traditionally been thought to be absent in atrial cardiomyocytes, recent studies suggest that t-tubules exist in the atria of large mammals. However, it is unclear whether regional differences in t-tubule organization exist, which define cardiomyocyte function across the atria. Objective: We sought to investigate regional t-tubule density in pig and rat atria, and the consequences for cardiomyocyte Ca2+ homeostasis. Methods and Results: In contrast to previous reports that t-tubules are absent in rat atria, we observed t- tubules in approximately one third of rat atrial cardiomyocytes, both in tissue cryosections and in isolated cardiomyocytes. In a minority (\approx10%) of atrial cardiomyocytes, the t-tubular network was well organized, with a transverse structure resembling that of ventricular cardiomyocytes. In both rat and pig atrial tissue, we observed higher t-tubule density in the epicardium than endocardium. Consistent with high variability in the distribution of t-tubules and Ca2+ channels among cells, L-type Ca2+ current amplitude was also highly variable, and steeply dependent on capacitance and t-tubule density. Accordingly, Ca2+ transients showed great variability in Ca2+ release synchrony. Simultaneous imaging of the cell membrane and Ca2+ transients confirmed t-tubule functionality. Results from mathematical modeling indicated that a transmural gradient in t-tubule organization and Ca2+ release kinetics supports synchronization of contraction across the atrial wall, and may underlie transmural differences in refractory period. Conclusions: T-tubule density is highly variable across the atria. We propose that higher t-tubule density in cells localized in the epicardium promotes synchronization of contraction across the atrial wall.