title: Calcium signalling microdomains and the t-tubular system in atrial mycoytes: potential roles in cardiac disease and arrhythmias.
abstract: The atria contribute 25% to ventricular stroke volume and are the site of the commonest cardiac arrhythmia, atrial fibrillation (AF). The initiation of contraction in the atria is similar to that in the ventricle involving a systolic rise of intracellular Ca(2+) concentration ([Ca(2+)](i)). There are, however, substantial inter-species differences in the way systolic Ca(2+) is regulated in atrial cells. These differences are a consequence of a well-developed and functionally relevant transverse (t)-tubule network in the atria of large mammals, including humans, and its virtual absence in smaller laboratory species such as the rat. Where T-tubules are absent, the systolic Ca(2+) transient results from a 'fire-diffuse-fire' sequential recruitment of Ca(2+) release sites from the cell edge to the centre and hence marked spatiotemporal heterogeneity of systolic Ca(2+). Conversely, the well-developed T-tubule network in large mammals ensures a near synchronous rise of [Ca(2+)](i). In addition to synchronizing the systolic rise of [Ca(2+)](i), the presence of T-tubules in the atria of large mammals, by virtue of localization of the L-type Ca(2+) channels and Na(+)-Ca(2+) exchanger antiporters on the T-tubules, may serve to, respectively, accelerate changes in the amplitude of the systolic Ca(2+) transient during inotropic manoeuvres and lower diastolic [Ca(2+)](i). On the other hand, the presence of T-tubules and hence wider cellular distribution of the Na(+)-Ca(2+) exchanger may predispose the atria of large mammals to Ca(2+)-dependent delayed afterdepolarizations (DADs); this may be a determining factor in why the atria of large mammals spontaneously develop and maintain AF.
authors: Unit of Cardiac Physiology, Manchester Academic Health Science Centre, Institute of Cardiovascular Science, University of Manchester, 3.23 Core Technology Facility, 46 Grafton Street, Manchester M13 9PT, UK.
authors: Andrew W
authors: AW
authors: Trafford
authors: Jessica D
authors: JD
authors: Clarke
authors: Mark A
authors: MA
authors: Richards
authors: David A
authors: DA
authors: Eisner
authors: Katharine M
authors: KM
authors: Dibb
mesh_terms: D000818:Animals; D001145:Arrhythmias, Cardiac / Q000209:etiology* / Q000378:metabolism; D001281:Atrial Fibrillation / Q000209:etiology; D020746:Calcium Channels, L-Type / Q000502:physiology; D020013:Calcium Signaling; D006325:Heart Atria; D006331:Heart Diseases / Q000209:etiology* / Q000378:metabolism; D006333:Heart Failure / Q000378:metabolism; D006801:Humans; D021962:Membrane Microdomains / Q000378:metabolism*; D009200:Myocardial Contraction; D032383:Myocytes, Cardiac / Q000502:physiology*; D012519:Sarcoplasmic Reticulum / Q000502:physiology*
chemical_list: D020746:Calcium Channels, L-Type