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 language | English |
|---|---|
| Pages (from-to) | 1255-1268 |
| Number of pages | 14 |
| Journal | Histology and Histopathology |
| Volume | 34 |
| Issue number | 11 |
| DOIs | |
| Publication status | Published - Nov 2019 |
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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 journal › Article
}
TY - JOUR
T1 - A sexy approach to pacemaking
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
PY - 2019/11
Y1 - 2019/11
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.
AB - 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.
KW - Arrhythmias
KW - Computer modelling
KW - Electrophysiology
KW - Gender
KW - Ion channels
KW - Pacemaker of the heart
KW - Sinoatrial
UR - http://www.scopus.com/inward/record.url?scp=85074461789&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=85074461789&partnerID=8YFLogxK
U2 - 10.14670/HH-18-115
DO - 10.14670/HH-18-115
M3 - Article
C2 - 30968943
AN - SCOPUS:85074461789
VL - 34
SP - 1255
EP - 1268
JO - Histology and Histopathology
JF - Histology and Histopathology
SN - 0213-3911
IS - 11
ER -