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

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dc.contributor.authorHoeker, Gregory S.en
dc.contributor.authorHood, A. R.en
dc.contributor.authorKatra, R. P.en
dc.contributor.authorPoelzing, Stevenen
dc.contributor.authorPogwizd, S. M.en
dc.contributor.departmentBiomedical Engineering and Mechanicsen
dc.contributor.departmentFralin Biomedical Research Instituteen
dc.contributor.departmentSchool of Biomedical Engineering and Sciencesen
dc.date.accessioned2017-02-03T15:15:27Zen
dc.date.available2017-02-03T15:15:27Zen
dc.date.issued2014-10-23en
dc.description.abstractCardioprotection in females, as observed in the setting of heart failure, has been attributed to sex differences in intracellular calcium handling and its modulation by b-adrenergic signaling. However, further studies examining sex differences in badrenergic 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 naı¨ve adult rabbits during b-adrenergic stimulation. The non-selective b-agonist isoproterenol (Iso) decreased AP duration (APD90), CaT duration (CaD80), and the decay constant of the CaT (t) in a dosedependent manner (1–316.2 nM), with a plateau at doses $31.6 nM. The Iso-induced changes in APD90 and t (but not CaD80) 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 b-adrenergic stimulation, particularly under conditions of increased demand (i.e. faster pacing rates and ‘‘maximal’’ levels of Iso effects), however this reduced badrenergic responsiveness of female hearts was associated with reduced arrhythmic activity.en
dc.description.versionPublished versionen
dc.format.extent? - ? (9) page(s)en
dc.format.mimetypeapplication/pdfen
dc.identifier.doihttps://doi.org/10.1371/journal.pone.0111411en
dc.identifier.issn1932-6203en
dc.identifier.issue10en
dc.identifier.urihttp://hdl.handle.net/10919/74923en
dc.identifier.volume9en
dc.language.isoenen
dc.publisherPLOSen
dc.relation.urihttp://gateway.webofknowledge.com/gateway/Gateway.cgi?GWVersion=2&SrcApp=PARTNER_APP&SrcAuth=LinksAMR&KeyUT=WOS:000343662800108&DestLinkType=FullRecord&DestApp=ALL_WOS&UsrCustomerID=930d57c9ac61a043676db62af60056c1en
dc.rightsCreative Commons Attribution 4.0 Internationalen
dc.rights.urihttp://creativecommons.org/licenses/by/4.0/en
dc.subjectrectifier potassium currenten
dc.subjectventricular myocytesen
dc.subjectgender-differencesen
dc.subjectrat-hearten
dc.subjectnervous-systemen
dc.subjectup-regulationen
dc.subjectrepolarizationen
dc.subjectfailureen
dc.subjectstimulationen
dc.subjectca2+en
dc.titleSex Differences in beta-Adrenergic Responsiveness of Action Potentials and Intracellular Calcium Handling in Isolated Rabbit Heartsen
dc.title.serialPLOS ONEen
dc.typeArticle - Refereeden
dc.type.dcmitypeTexten
pubs.organisational-group/Virginia Techen
pubs.organisational-group/Virginia Tech/All T&R Facultyen
pubs.organisational-group/Virginia Tech/Faculty of Health Sciencesen
pubs.organisational-group/Virginia Tech/University Research Institutesen
pubs.organisational-group/Virginia Tech/University Research Institutes/Virginia Tech Carilion Research Instituteen

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