Prolonged AP duration by estrogen is independent of
INaL
The rapid and inward Na+ currents determine the
dynamics of the ascending branch of AP (Vikram et al., 2017). On the
other hand, I NaL, a small and sustained
Na+ influx, lasts for hundreds of milliseconds and
maintains the plateau phase of AP with inward calcium current (Portero
et al., 2017; Zaza & Rocchetti, 2013). Therefore, we analyzed the AP to
explore the relationship between estrogen, sodium currents and AP.
Estrogen at medium concentration prolonged the AP duration, which may
explain why women have longer AP duration and longer QTc interval than
men of the same age (Salem, Alexandre, Bachelot, & Funck-Brentano,
2016). It seems that the prolonged AP duration caused by estrogen was
independent of I NaL which is likely that the
treatment time of estrogen is too short to increase theI NaL. Short-term estrogen treatment failed to
amplify I NaL, but increased a certain amount ofI NaL. With the prolongation of estrogen treatment
time, I NaL increased significantly, just as theI NaL in female mice exposed to estrogen for a
long time is larger than that in male mice (Lowe et al., 2012). In
addition, the prolonged AP duration induced by estrogen may be
associated with the increase in calcium currents (Papp et al., 2017; X.
Yang et al., 2018).
Notably, the shortened AP duration induced by stress was abolished by
estrogen. Although β-adrenergic overstimulation increasedI NaL, however, it did not prolong the AP
duration. The shortened AP duration might be caused by the increase and
rapid inactivation of the L-type calcium current in the early stage of
repolarization following β-adrenergic activation (Sala et al., 2018).
Also, ISO treatment increased slow delayed rectifier potassium current
which will shorten the AP duration (Banyasz et al., 2014; Gong JQX,
2020). During the occurrence of heart failure, the electrophysiological
remodeling of the myocardium is manifested by an increase inI NaL and the prolongation of AP duration, which
may be related to time and the degree of stress (B. Hegyi et al., 2019)
. So, under acute stress, it is likely that estrogen may inversely
regulates L-type calcium current or potassium currents to prolong the AP
duration while reducing the increase in I NaL.
Therefore, we will further study the regulation of estrogen on calcium
and potassium channels under stress.