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A sexy approach to pacemaking: differences in function and molecular make up of the sinoatrial node

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dc.contributor.authorDoris, Ursula
dc.contributor.authorKharche, Sanjay
dc.contributor.authorPetkova, Maria
dc.contributor.authorBorbas, Balint
dc.contributor.authorLogantha, Sunil Jit R.J.
dc.contributor.authorFedorenko, Olga
dc.contributor.authorMaczewski, MIchal
dc.contributor.authorMackiewicz, Urszula
dc.contributor.authorZhang, Yu
dc.contributor.authorChahal, Anwar
dc.contributor.authorD’Souza, Alicia
dc.contributor.authorAtkinson, Andrew J.
dc.contributor.authorDobrzynski, Halina
dc.contributor.authorYanni, Joseph
dc.date.accessioned2022-10-24T15:25:54Z
dc.date.available2022-10-24T15:25:54Z
dc.date.issued2019
dc.description.abstractBackground. Functional properties of the sinoatrial node (SAN) are known to differ between sexes. Women have higher resting and intrinsic heart rates. Sex determines the risk of developing certain arrhythmias such as sick sinus syndrome, which occur more often in women. We believe that a major contributor to these differences is in gender specific ion channel expression. Methods. qPCR was used to compare ion channel gene expression in the SAN and right atrium (RA) between male and female rats. Histology, immunohistochemistry and signal intensity analysis were used to locate the SAN and determine abundance of ion channels. The effect of nifedipine on extracellular potential recording was used to determine differences in beating rate between sexes. Results. mRNAs for Ca v1.3, Kir3.1, and Nkx2-5, as well as expression of the L-Type Ca 2+ channel protein, were higher in the female SAN. Females had significantly higher intrinsic heart rates and the effect of nifedipine on isolated SAN preparations was significantly greater in male SAN. Computer modelling using a SAN cell model demonstrated a higher propensity of pacemaker-related arrhythmias in females. Conclusion. This study has identified key differences in the expression of Ca v 1.3, K ir 3.1 and Nkx2-5 at mRNA and/or protein levels between male and female SAN. Cav1.3 plays an important role in the pacemaker function of the SAN, therefore the higher intrinsic heart rate of the female SAN could be caused by the higher expression of Ca v 1.3. The differences identified in this study advance our understanding of sex differences in cardiac electrophysiology and arrhythmias.es
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dc.format.extent14es
dc.identifier.citationHistology and Histopathology Vol. 34, nÂş 11 (2019
dc.identifier.doihttps://doi.org/10.14670/HH-18-115
dc.identifier.issn0213-3911
dc.identifier.issn1699-5848
dc.identifier.urihttp://hdl.handle.net/10201/124844
dc.languageenges
dc.publisherUniversidad de Murcia, Departamento de Biologia Celular e Histiologiaes
dc.relationSin financiaciĂłn externa a la Universidades
dc.rightsinfo:eu-repo/semantics/openAccesses
dc.rightsAttribution-NonCommercial-NoDerivatives 4.0 Internacional*
dc.rights.urihttp://creativecommons.org/licenses/by-nc-nd/4.0/*
dc.subjectIon channelses
dc.subjectArrhythmiases
dc.subjectPacemaker of the heartes
dc.subjectSinoatriales
dc.subjectGenderes
dc.subjectElectrophysiologyes
dc.subjectComputer modellinges
dc.subject.otherCDU::6 - Ciencias aplicadas::61 - Medicina::616 - PatologĂ­a. Medicina clĂ­nica. OncologĂ­aes
dc.titleA sexy approach to pacemaking: differences in function and molecular make up of the sinoatrial nodees
dc.typeinfo:eu-repo/semantics/articlees
dspace.entity.typePublicationes
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Histology and histopathology Vol.34,nÂş11 (2019)