Calcium signalling microdomains and the t-tubular system in atrial mycoytes: potential roles in cardiac disease and arrhythmias

• Published in: Cardiovascular research 2013-05, Vol.98 (2), p.192-203
• Main Authors: Trafford, Andrew W, Clarke, Jessica D, Richards, Mark A, Eisner, David A, Dibb, Katharine M
• Format: Article
• Language: English
• Subjects: Animals; Arrhythmias, Cardiac - etiology; Arrhythmias, Cardiac - metabolism; Atrial Fibrillation - etiology; Calcium Channels, L-Type - physiology; Calcium Signaling; Heart Atria; Heart Diseases - etiology; Heart Diseases - metabolism; Heart Failure - metabolism; Humans; Membrane Microdomains - metabolism; Myocardial Contraction; Myocytes, Cardiac - physiology; Sarcoplasmic Reticulum - physiology
• ISSN: 0008-6363; 1755-3245
• DOI: 10.1093/cvr/cvt018

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.