A sexy approach to pacemaking: differences in function and molecular make up of the sinoatrial node
2018
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 Cav1.3, 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 Cav1.3, Kir
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 Cav1.3. The differences
identified in this study advance our understanding of sex
differences in cardiac electrophysiology and
arrhythmias.
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