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

Ursula Doris, Sanjay Kharche, Maria Petkova, Balint Borbas, Sunil Jit R.J. Logantha, Olga Fedorenko, Michal Maczewski, Urszula Mackiewicz, Yu Zhang, Anwar Chahal, Alicia D’souza, Andrew J. Atkinson, Halina Dobrzynski, Joseph Yanni

Research output: Contribution to journalArticle

Abstract

Background. 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 Cav 1.3, Kir 3.1, and Nkx2-5, as well as expression of the L-Type Ca2+ 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 Cav 1.3, Kir 3.1 and Nkx2-5 at mRNA and/or protein levels between male and female SAN. Cav 1.3 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 Cav 1.3. The differences identified in this study advance our understanding of sex differences in cardiac electrophysiology and arrhythmias.

Original languageEnglish
Pages (from-to)1255-1268
Number of pages14
JournalHistology and Histopathology
Volume34
Issue number11
DOIs
Publication statusPublished - Nov 2019

Fingerprint

Sinoatrial Node
Ion Channels
Cardiac Arrhythmias
Heart Rate
Nifedipine
Cardiac Electrophysiology
Sick Sinus Syndrome
Messenger RNA
Heart Atria
Sex Characteristics
Histology
Proteins
Immunohistochemistry
Gene Expression

Keywords

  • Arrhythmias
  • Computer modelling
  • Electrophysiology
  • Gender
  • Ion channels
  • Pacemaker of the heart
  • Sinoatrial

ASJC Scopus subject areas

  • Pathology and Forensic Medicine
  • Histology

Cite this

A sexy approach to pacemaking : Differences in function and molecular make up of the sinoatrial node. / Doris, Ursula; Kharche, Sanjay; Petkova, Maria; Borbas, Balint; Logantha, Sunil Jit R.J.; Fedorenko, Olga; Maczewski, Michal; Mackiewicz, Urszula; Zhang, Yu; Chahal, Anwar; D’souza, Alicia; Atkinson, Andrew J.; Dobrzynski, Halina; Yanni, Joseph.

In: Histology and Histopathology, Vol. 34, No. 11, 11.2019, p. 1255-1268.

Research output: Contribution to journalArticle

Doris, U, Kharche, S, Petkova, M, Borbas, B, Logantha, SJRJ, Fedorenko, O, Maczewski, M, Mackiewicz, U, Zhang, Y, Chahal, A, D’souza, A, Atkinson, AJ, Dobrzynski, H & Yanni, J 2019, 'A sexy approach to pacemaking: Differences in function and molecular make up of the sinoatrial node', Histology and Histopathology, vol. 34, no. 11, pp. 1255-1268. https://doi.org/10.14670/HH-18-115
Doris, Ursula ; Kharche, Sanjay ; Petkova, Maria ; Borbas, Balint ; Logantha, Sunil Jit R.J. ; Fedorenko, Olga ; Maczewski, Michal ; Mackiewicz, Urszula ; Zhang, Yu ; Chahal, Anwar ; D’souza, Alicia ; Atkinson, Andrew J. ; Dobrzynski, Halina ; Yanni, Joseph. / A sexy approach to pacemaking : Differences in function and molecular make up of the sinoatrial node. In: Histology and Histopathology. 2019 ; Vol. 34, No. 11. pp. 1255-1268.
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abstract = "Background. 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 Cav 1.3, Kir 3.1, and Nkx2-5, as well as expression of the L-Type Ca2+ 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 Cav 1.3, Kir 3.1 and Nkx2-5 at mRNA and/or protein levels between male and female SAN. Cav 1.3 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 Cav 1.3. The differences identified in this study advance our understanding of sex differences in cardiac electrophysiology and arrhythmias.",
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T2 - Differences in function and molecular make up of the sinoatrial node

AU - Doris, Ursula

AU - Kharche, Sanjay

AU - Petkova, Maria

AU - Borbas, Balint

AU - Logantha, Sunil Jit R.J.

AU - Fedorenko, Olga

AU - Maczewski, Michal

AU - Mackiewicz, Urszula

AU - Zhang, Yu

AU - Chahal, Anwar

AU - D’souza, Alicia

AU - Atkinson, Andrew J.

AU - Dobrzynski, Halina

AU - Yanni, Joseph

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N2 - Background. 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 Cav 1.3, Kir 3.1, and Nkx2-5, as well as expression of the L-Type Ca2+ 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 Cav 1.3, Kir 3.1 and Nkx2-5 at mRNA and/or protein levels between male and female SAN. Cav 1.3 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 Cav 1.3. The differences identified in this study advance our understanding of sex differences in cardiac electrophysiology and arrhythmias.

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KW - Ion channels

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