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Direct measurements of SR free Ca reveal the mechanism underlying the transient effects of RyR potentiation under physiological conditions

Greensmith, DJ, Galli, GLJ, Trafford, AW and Eisner, DA 2014, 'Direct measurements of SR free Ca reveal the mechanism underlying the transient effects of RyR potentiation under physiological conditions' , Cardiovascular research, 103 (4) , pp. 554-563.

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Abstract

AIMS Most of the calcium that activates contraction is released from the sarcoplasmic reticulum (SR) through the ryanodine receptor (RyR). It is controversial whether activators of the RyR produce a maintained increase in the amplitude of the systolic Ca transient. We therefore aimed to examine the effects of activation of the RyR in large animals under conditions designed to be as physiological as possible while simultaneously measuring SR and cytoplasmic Ca. METHODS AND RESULTS Experiments were performed on ventricular myocytes from canine and ovine hearts. Cytoplasmic Ca was measured with fluo-3 and SR Ca with mag-fura-2. Application of caffeine resulted in a brief increase in the amplitude of the systolic Ca transient accompanied by an increase of action potential duration. These effects disappeared with a rate constant of ∼3 s(-1). Similar effects were seen in cells taken from sheep in which heart failure had been induced by rapid pacing. The decrease of Ca transient amplitude was accompanied by a decrease of SR Ca content. During this phase, the maximum (end-diastolic) SR Ca content fell while the minimum systolic increased. CONCLUSIONS This study shows that, under conditions designed to be as physiological as possible, potentiation of RyR opening has no maintained effect on the systolic Ca transient. This result makes it unlikely that potentiation of the RyR has a maintained role in positive inotropy.

Item Type: Article
Themes: Health and Wellbeing
Subjects outside of the University Themes
Schools: Schools > School of Environment and Life Sciences > Biomedical Research Centre
Journal or Publication Title: Cardiovascular research
Publisher: Oxford University Press
Refereed: Yes
ISSN: 1755-3245
Related URLs:
Funders: British Heart Foundation
Depositing User: D Greensmith
Date Deposited: 21 Jan 2015 11:51
Last Modified: 23 Jan 2015 10:00
URI: http://usir.salford.ac.uk/id/eprint/33358

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