The impact of t-tubule disruption on excitation-contraction coupling and calcium handling in rat ventricular trabeculae

Show simple item record Power, Amelia en Kaur, Sarbjot en Dyer, C en Ward, Marie-Louise en
dc.coverage.spatial Hamburg, Germany en 2018-10-16T22:17:20Z en 2017-07-24 en
dc.identifier.issn 0022-2828 en
dc.identifier.uri en
dc.description.abstract Background: Reduced contractility is a hallmark of failing hearts, often linked to depressed Ca2+ transients, since Ca2+ is the key activator of contraction. Impaired excitation-contraction coupling has been observed in conjunction with structural alterations to the t-tubular system. However, many sub-cellular changes occur in heart failure, making it difficult to determine the contribution of disrupted t-tubules. Our aim was to quantify the impact of detubulation on Ca2+ handling and contraction in otherwise healthy ventricular tissue. Methods: Measurement of [Ca2+]i (fura-2) and stress were made in RV trabeculae from rat hearts before and after detubulation following formamide treatment (1.5 M, 5 min). The effect of detubulation on two important regulatory mechanisms was also investigated: the response to stretch, and to β-adrenergic stimulation (0.1 μM isoproterenol). Results: De-tubulation of trabeculae slowed the time course of the Ca2+ transients and twitch force: time-to-peak, maximum rate-of-rise, and relaxation were prolonged in both. The slow force response to stretch was decreased following detubulation, and the response to β-adrenergic activation blunted. Conclusions: This study enabled us to examine the effect of detubulation on Ca2+ transients and twitch force in tissue from non-failing hearts in which expression of the different Ca2+ handling proteins was not altered by any disease process. Our results demonstrate the importance of an intact t-tubular system on the kinetics of excitation-contraction coupling, as well as on mechanisms that regulate contractility in vivo: the response to stretch and β-adrenergic stimulation. en
dc.publisher Academic Press en
dc.relation.ispartof 34th Annual Meeting, European Section of the International Society for Heart Research en
dc.relation.ispartofseries Journal of Molecular and Cellular Cardiology en
dc.rights Items in ResearchSpace are protected by copyright, with all rights reserved, unless otherwise indicated. Previously published items are made available in accordance with the copyright policy of the publisher. en
dc.rights.uri en
dc.title The impact of t-tubule disruption on excitation-contraction coupling and calcium handling in rat ventricular trabeculae en
dc.type Conference Item en
pubs.begin-page 42 en
pubs.volume 109 en
dc.rights.holder Copyright: The author en
pubs.end-page 42 en
pubs.finish-date 2017-07-27 en
pubs.start-date 2017-07-24 en
dc.rights.accessrights en
pubs.subtype Proceedings en
pubs.elements-id 654743 en Medical and Health Sciences en Medical Sciences en Physiology Division en
pubs.record-created-at-source-date 2017-08-29 en

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