T. Nakajima et al., Antiarrhythmic effect and its underlying ionic mechanism of 17 beta-estradiol in cardiac myocytes, BR J PHARM, 127(2), 1999, pp. 429-440
1 The effects of oestrogens on action potential and membrane currents were
examined in single guinea-pig atrial myocytes.
2 17 beta-estradiol (3-10 mu M) Shortened the action potential duration wit
hout significant changes in the resting membrane potential. E-4031 (1 mu M)
markedly prolonged the action potential duration and induced early afterde
polarization, and 17 beta-estradiol (10 mu M) abolished it.
3 When cells were perfused in isoproterenol-containing solution, action pot
entials due to abnormal automaticity caused by membrane depolarization deve
loped, and were also inhibited by 17 beta-estradiol.
4 Under voltage clamp conditions, the voltage-dependent Ca2+ currents consi
sted of both T-(I-Ca.T) and L-type (I-Ca.L). 17 beta-estradiol reduced I-Ca
.L concentration-dependently, while it (10 mu M) suppressed I-Ca.T only by
approximately 10%. 17 beta-estradiol did not affect time courses of I-Ca.L
inactivation, but it shifted the steady-state inactivation curve to more ne
gative potentials.
5 17 beta-estradiol (10 mu M) did not affect the time-dependent K+ current
(IK), referred to as IK, and I-Ks, and inwardly rectifying K+; current. How
ever, 17 beta-estradiol (30 mu M) or diethylstilbestrol (10 mu M) inhibited
Ki currents.
6 DES and ethinylestradiol (EES) also suppressed I-Ca.L but testosterone an
d progesterone failed to inhibit I-Ca.L The potency of the inhibitory effec
t on I-Ca.L was DES > EES > 17 beta-estradiol.
7 17 beta-estradiol and DES also inhibited the cyclic AMP-enhanced I-Ca.L,
but cyclic GMP in the pipette or pretreatment of L-NAME could not block the
effects of oestrogen on I-Ca.L
8 These results suggest that oestrogen specifically has antiarrhythmic effe
cts, possibly by acting the L-type Ca2+ channels. The antiarrhythmic effect
s of oestrogens may contribute to the cardioprotective actions of oestrogen
s.