Cargando…
Direct measurements of SR free Ca reveal the mechanism underlying the transient effects of RyR potentiation under physiological conditions
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...
Autores principales: | , , , |
---|---|
Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Oxford University Press
2014
|
Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4145011/ https://www.ncbi.nlm.nih.gov/pubmed/24947416 http://dx.doi.org/10.1093/cvr/cvu158 |
_version_ | 1782332115675774976 |
---|---|
author | Greensmith, David J. Galli, Gina L.J. Trafford, Andrew W. Eisner, David A. |
author_facet | Greensmith, David J. Galli, Gina L.J. Trafford, Andrew W. Eisner, David A. |
author_sort | Greensmith, David J. |
collection | PubMed |
description | 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. |
format | Online Article Text |
id | pubmed-4145011 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2014 |
publisher | Oxford University Press |
record_format | MEDLINE/PubMed |
spelling | pubmed-41450112014-08-27 Direct measurements of SR free Ca reveal the mechanism underlying the transient effects of RyR potentiation under physiological conditions Greensmith, David J. Galli, Gina L.J. Trafford, Andrew W. Eisner, David A. Cardiovasc Res Original Articles 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. Oxford University Press 2014-09-01 2014-06-19 /pmc/articles/PMC4145011/ /pubmed/24947416 http://dx.doi.org/10.1093/cvr/cvu158 Text en © The Author 2014. Published by Oxford University Press on behalf of the European Society of Cardiology. http://creativecommons.org/licenses/by/4.0/ This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/4.0/), which permits unrestricted reuse, distribution, and reproduction in any medium, provided the original work is properly cited. |
spellingShingle | Original Articles Greensmith, David J. Galli, Gina L.J. Trafford, Andrew W. Eisner, David A. Direct measurements of SR free Ca reveal the mechanism underlying the transient effects of RyR potentiation under physiological conditions |
title | Direct measurements of SR free Ca reveal the mechanism underlying the transient effects of RyR potentiation under physiological conditions |
title_full | Direct measurements of SR free Ca reveal the mechanism underlying the transient effects of RyR potentiation under physiological conditions |
title_fullStr | Direct measurements of SR free Ca reveal the mechanism underlying the transient effects of RyR potentiation under physiological conditions |
title_full_unstemmed | Direct measurements of SR free Ca reveal the mechanism underlying the transient effects of RyR potentiation under physiological conditions |
title_short | Direct measurements of SR free Ca reveal the mechanism underlying the transient effects of RyR potentiation under physiological conditions |
title_sort | direct measurements of sr free ca reveal the mechanism underlying the transient effects of ryr potentiation under physiological conditions |
topic | Original Articles |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4145011/ https://www.ncbi.nlm.nih.gov/pubmed/24947416 http://dx.doi.org/10.1093/cvr/cvu158 |
work_keys_str_mv | AT greensmithdavidj directmeasurementsofsrfreecarevealthemechanismunderlyingthetransienteffectsofryrpotentiationunderphysiologicalconditions AT galliginalj directmeasurementsofsrfreecarevealthemechanismunderlyingthetransienteffectsofryrpotentiationunderphysiologicalconditions AT traffordandreww directmeasurementsofsrfreecarevealthemechanismunderlyingthetransienteffectsofryrpotentiationunderphysiologicalconditions AT eisnerdavida directmeasurementsofsrfreecarevealthemechanismunderlyingthetransienteffectsofryrpotentiationunderphysiologicalconditions |