title: Variable t-tubule organization and Ca2+ homeostasis across the atria.
abstract: Although t-tubules have traditionally been thought to be absent in atrial cardiomyocytes, recent studies have suggested that t-tubules exist in the atria of large mammals. However, it is unclear whether regional differences in t-tubule organization exist that define cardiomyocyte function across the atria. We sought to investigate regional t-tubule density in pig and rat atria and the consequences for cardiomyocyte Ca(2+) homeostasis. We observed t-tubules in approximately one-third of rat atrial cardiomyocytes, in both tissue cryosections and isolated cardiomyocytes. In a minority (≈10%) 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 in the endocardium. Consistent with high variability in the distribution of t-tubules and Ca(2+) channels among cells, L-type Ca(2+) current amplitude was also highly variable and steeply dependent on capacitance and t-tubule density. Accordingly, Ca(2+) transients showed great variability in Ca(2+) release synchrony. Simultaneous imaging of the cell membrane and Ca(2+) transients confirmed t-tubule functionality. Results from mathematical modeling indicated that a transmural gradient in t-tubule organization and Ca(2+) release kinetics supports synchronization of contraction across the atrial wall and may underlie transmural differences in the refractory period. In conclusion, our results indicate that t-tubule density is highly variable across the atria. We propose that higher t-tubule density in cells localized in the epicardium may promote synchronization of contraction across the atrial wall.
authors.affiliation: Institute for Experimental Medical Research, Oslo University Hospital and University of Oslo, Oslo, Norway; KG Jebsen Cardiac Research Center and Center for Heart Failure Research, University of Oslo, Oslo, Norway; michael.frisk@medisin.uio.no.
authors.forename: Michael
authors.initials: M
authors.lastname: Frisk
authors.affiliation: Center for Biomedical Computing, Simula Research Laboratory, Oslo, Norway; and Center for Cardiological Innovation, Oslo University Hospital, Oslo, Norway.
authors.forename: Jussi T
authors.initials: JT
authors.lastname: Koivumäki
authors.affiliation: Institute for Experimental Medical Research, Oslo University Hospital and University of Oslo, Oslo, Norway; KG Jebsen Cardiac Research Center and Center for Heart Failure Research, University of Oslo, Oslo, Norway;
authors.forename: Per A
authors.initials: PA
authors.lastname: Norseng
authors.affiliation: Center for Biomedical Computing, Simula Research Laboratory, Oslo, Norway; and Center for Cardiological Innovation, Oslo University Hospital, Oslo, Norway.
authors.forename: Mary M
authors.initials: MM
authors.lastname: Maleckar
authors.affiliation: Institute for Experimental Medical Research, Oslo University Hospital and University of Oslo, Oslo, Norway; KG Jebsen Cardiac Research Center and Center for Heart Failure Research, University of Oslo, Oslo, Norway;
authors.forename: Ole M
authors.initials: OM
authors.lastname: Sejersted
authors.affiliation: Institute for Experimental Medical Research, Oslo University Hospital and University of Oslo, Oslo, Norway; KG Jebsen Cardiac Research Center and Center for Heart Failure Research, University of Oslo, Oslo, Norway;
authors.forename: William E
authors.initials: WE
authors.lastname: Louch
mesh_terms: D000200:Action Potentials; D000818:Animals; D002118:Calcium / Q000378:metabolism*; D020746:Calcium Channels, L-Type / Q000378:metabolism; D020013:Calcium Signaling; D004699:Endocardium / Q000166:cytology / Q000378:metabolism; D006325:Heart Atria / Q000166:cytology / Q000378:metabolism; D006706:Homeostasis; D008955:Models, Cardiovascular; D032383:Myocytes, Cardiac / Q000166:cytology / Q000378:metabolism* / Q000502:physiology; D009928:Organ Specificity; D010496:Pericardium / Q000166:cytology / Q000378:metabolism; D051381:Rats; D017208:Rats, Wistar; D012508:Sarcolemma / Q000378:metabolism / Q000648:ultrastructure*; D013552:Swine
chemical_list: D020746:Calcium Channels, L-Type; D002118:Calcium
keywords: Ca2+ handling; confocal microscopy; excitation-contraction coupling; membrane structure; three-dimensional reconstruction