title: Characterization of an extensive transverse tubular network in sheep atrial myocytes and its depletion in heart failure.
abstract: BACKGROUND
  In ventricular myocytes, the majority of structures that couple excitation to the systolic rise of Ca(2+) are located at the transverse tubular (t-tubule) membrane. In the failing ventricle, disorganization of t-tubules disrupts excitation contraction coupling. The t-tubule membrane is virtually absent in the atria of small mammals resulting in spatiotemporally distinct profiles of intracellular Ca(2+) release on stimulation in atrial and ventricular cells. The aims of this study were to determine (i) whether atrial myocytes from a large mammal (sheep) possess t-tubules, (ii) whether these are functionally important, and (iii) whether they are disrupted in heart failure.
  
  
  RESULTS
  Sheep left atrial myocytes were stained with di-4-ANEPPS. Nearly all control cells had an extensive t-tubule network resulting in each voxel in the cell being nearer to a membrane (sarcolemma or t-tubule) than would otherwise be the case. T-tubules decrease the distance of 50% of voxels from a membrane from 3.35 + or - 0.15 to 0.88 + or- 0.04 microm. During depolarization, intracellular Ca(2+) rises simultaneously at the cell periphery and center. In heart failure induced by rapid ventricular pacing, there was an almost complete loss of atrial t-tubules. The distance of 50% of voxels from a membrane increased to 2.04 + or - 0.08 microm, and there was a loss of early Ca(2+) release from the cell center.
  
  
  CONCLUSIONS
  Sheep atrial myocytes possess a substantial t-tubule network that synchronizes the systolic Ca(2+) transient. In heart failure, this network is markedly disrupted. This may play an important role in changes of atrial function in heart failure.
authors.affiliation: Unit of Cardiac Physiology, University of Manchester, Core Technology Facility, 46 Grafton St, Manchester M13 9NT, United Kingdom. katharine.dibb@man.ac.uk
authors.forename: Katharine M
authors.initials: KM
authors.lastname: Dibb
authors.forename: Jessica D
authors.initials: JD
authors.lastname: Clarke
authors.forename: Margaux A
authors.initials: MA
authors.lastname: Horn
authors.forename: Mark A
authors.initials: MA
authors.lastname: Richards
authors.forename: Helen K
authors.initials: HK
authors.lastname: Graham
authors.forename: David A
authors.initials: DA
authors.lastname: Eisner
authors.forename: Andrew W
authors.initials: AW
authors.lastname: Trafford
mesh_terms: D000818:Animals; D016279:Atrial Function, Left; D020013:Calcium Signaling; D002304:Cardiac Pacing, Artificial; D004195:Disease Models, Animal; D005456:Fluorescent Dyes; D006325:Heart Atria / Q000378:metabolism; D006333:Heart Failure / Q000378:metabolism* / Q000473:pathology / Q000503:physiopathology; D007091:Image Processing, Computer-Assisted; D018613:Microscopy, Confocal; D009200:Myocardial Contraction; D032383:Myocytes, Cardiac / Q000378:metabolism* / Q000473:pathology; D011726:Pyridinium Compounds; D051381:Rats; D012508:Sarcolemma / Q000378:metabolism* / Q000473:pathology; D012756:Sheep; D016277:Ventricular Function, Left
chemical_list: D005456:Fluorescent Dyes; D011726:Pyridinium Compounds; C050019:1-(3-sulfonatopropyl)-4-(beta)(2-(di-n-butylamino)-6-naphthylvinyl)pyridinium betaine