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Sex Differences in β-Adrenergic Responsiveness of Action Potentials and Intracellular Calcium Handling in Isolated Rabbit Hearts

Cardioprotection in females, as observed in the setting of heart failure, has been attributed to sex differences in intracellular calcium handling and its modulation by β-adrenergic signaling. However, further studies examining sex differences in β-adrenergic responsiveness have yielded inconsistent...

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Autores principales: Hoeker, Gregory S., Hood, Ashleigh R., Katra, Rodolphe P., Poelzing, Steven, Pogwizd, Steven M.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Public Library of Science 2014
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4207827/
https://www.ncbi.nlm.nih.gov/pubmed/25340795
http://dx.doi.org/10.1371/journal.pone.0111411
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author Hoeker, Gregory S.
Hood, Ashleigh R.
Katra, Rodolphe P.
Poelzing, Steven
Pogwizd, Steven M.
author_facet Hoeker, Gregory S.
Hood, Ashleigh R.
Katra, Rodolphe P.
Poelzing, Steven
Pogwizd, Steven M.
author_sort Hoeker, Gregory S.
collection PubMed
description Cardioprotection in females, as observed in the setting of heart failure, has been attributed to sex differences in intracellular calcium handling and its modulation by β-adrenergic signaling. However, further studies examining sex differences in β-adrenergic responsiveness have yielded inconsistent results and have mostly been limited to studies of contractility, ion channel function, or calcium handling alone. Given the close interaction of the action potential (AP) and intracellular calcium transient (CaT) through the process of excitation-contraction coupling, the need for studies exploring the relationship between agonist-induced AP and calcium handling changes in female and male hearts is evident. Thus, the aim of this study was to use optical mapping to examine sex differences in ventricular APs and CaTs measured simultaneously from Langendorff-perfused hearts isolated from naïve adult rabbits during β-adrenergic stimulation. The non-selective β-agonist isoproterenol (Iso) decreased AP duration (APD(90)), CaT duration (CaD(80)), and the decay constant of the CaT (τ) in a dose-dependent manner (1–316.2 nM), with a plateau at doses ≥31.6 nM. The Iso-induced changes in APD(90) and τ (but not CaD(80)) were significantly smaller in female than male hearts. These sex differences were more significant at faster (5.5 Hz) than resting rates (3 Hz). Treatment with Iso led to the development of spontaneous calcium release (SCR) with a dose threshold of 31.6 nM. While SCR occurrence was similar in female (49%) and male (53%) hearts, the associated ectopic beats had a lower frequency of occurrence (16% versus 40%) and higher threshold (100 nM versus 31.6 nM) in female than male hearts (p<0.05). In conclusion, female hearts had a decreased capacity to respond to β-adrenergic stimulation, particularly under conditions of increased demand (i.e. faster pacing rates and “maximal” levels of Iso effects), however this reduced β-adrenergic responsiveness of female hearts was associated with reduced arrhythmic activity.
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spelling pubmed-42078272014-10-27 Sex Differences in β-Adrenergic Responsiveness of Action Potentials and Intracellular Calcium Handling in Isolated Rabbit Hearts Hoeker, Gregory S. Hood, Ashleigh R. Katra, Rodolphe P. Poelzing, Steven Pogwizd, Steven M. PLoS One Research Article Cardioprotection in females, as observed in the setting of heart failure, has been attributed to sex differences in intracellular calcium handling and its modulation by β-adrenergic signaling. However, further studies examining sex differences in β-adrenergic responsiveness have yielded inconsistent results and have mostly been limited to studies of contractility, ion channel function, or calcium handling alone. Given the close interaction of the action potential (AP) and intracellular calcium transient (CaT) through the process of excitation-contraction coupling, the need for studies exploring the relationship between agonist-induced AP and calcium handling changes in female and male hearts is evident. Thus, the aim of this study was to use optical mapping to examine sex differences in ventricular APs and CaTs measured simultaneously from Langendorff-perfused hearts isolated from naïve adult rabbits during β-adrenergic stimulation. The non-selective β-agonist isoproterenol (Iso) decreased AP duration (APD(90)), CaT duration (CaD(80)), and the decay constant of the CaT (τ) in a dose-dependent manner (1–316.2 nM), with a plateau at doses ≥31.6 nM. The Iso-induced changes in APD(90) and τ (but not CaD(80)) were significantly smaller in female than male hearts. These sex differences were more significant at faster (5.5 Hz) than resting rates (3 Hz). Treatment with Iso led to the development of spontaneous calcium release (SCR) with a dose threshold of 31.6 nM. While SCR occurrence was similar in female (49%) and male (53%) hearts, the associated ectopic beats had a lower frequency of occurrence (16% versus 40%) and higher threshold (100 nM versus 31.6 nM) in female than male hearts (p<0.05). In conclusion, female hearts had a decreased capacity to respond to β-adrenergic stimulation, particularly under conditions of increased demand (i.e. faster pacing rates and “maximal” levels of Iso effects), however this reduced β-adrenergic responsiveness of female hearts was associated with reduced arrhythmic activity. Public Library of Science 2014-10-23 /pmc/articles/PMC4207827/ /pubmed/25340795 http://dx.doi.org/10.1371/journal.pone.0111411 Text en © 2014 Hoeker et al http://creativecommons.org/licenses/by/4.0/ This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are properly credited.
spellingShingle Research Article
Hoeker, Gregory S.
Hood, Ashleigh R.
Katra, Rodolphe P.
Poelzing, Steven
Pogwizd, Steven M.
Sex Differences in β-Adrenergic Responsiveness of Action Potentials and Intracellular Calcium Handling in Isolated Rabbit Hearts
title Sex Differences in β-Adrenergic Responsiveness of Action Potentials and Intracellular Calcium Handling in Isolated Rabbit Hearts
title_full Sex Differences in β-Adrenergic Responsiveness of Action Potentials and Intracellular Calcium Handling in Isolated Rabbit Hearts
title_fullStr Sex Differences in β-Adrenergic Responsiveness of Action Potentials and Intracellular Calcium Handling in Isolated Rabbit Hearts
title_full_unstemmed Sex Differences in β-Adrenergic Responsiveness of Action Potentials and Intracellular Calcium Handling in Isolated Rabbit Hearts
title_short Sex Differences in β-Adrenergic Responsiveness of Action Potentials and Intracellular Calcium Handling in Isolated Rabbit Hearts
title_sort sex differences in β-adrenergic responsiveness of action potentials and intracellular calcium handling in isolated rabbit hearts
topic Research Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4207827/
https://www.ncbi.nlm.nih.gov/pubmed/25340795
http://dx.doi.org/10.1371/journal.pone.0111411
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