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Antiarrhythmic effect and its underlying ionic mechanism of 17beta-estradiol in cardiac myocytes
T Nakajima1, K Iwasawa, H Oonuma
1The 2nd Department of Internal Medicine, University of Tokyo, Japan.
Abstract:
1. The effects of oestrogens on action potential and membrane currents were examined in single guinea-pig atrial myocytes. 2. 17Beta-estradiol (3-10 microM) shortened the action potential duration without significant changes in the resting membrane potential. E-4031 (1 microM) markedly prolonged the action potential duration and induced early afterdepolarization, and 17beta-estradiol (10 microM) abolished it. 3. When cells were perfused in isoproterenol-containing solution, action potentials due to abnormal automaticity caused by membrane depolarization developed, and were also inhibited by 17beta-estradiol. 4. Under voltage clamp conditions, the voltage-dependent Ca2+ currents consisted of both T-(I(Ca,T)) and L-type (I(Ca,L)). 17Beta-estradiol reduced I(Ca,L) concentration-dependently, while it (10 microM) suppressed I(Ca,T) only by approximately 10%. 17Beta-estradiol did not affect time courses of I(Ca,L) inactivation, but it shifted the steady-state inactivation curve to more negative potentials. 5. 17Beta-estradiol (10 microM) did not affect the time-dependent K+ current (I(K)), referred to as I(Kr) and I(Ks) and inwardly rectifying K+ current. However, 17beta-estradiol (30 microM) or diethylstilbestrol (10 microM) inhibited K+ currents. 6. DES and ethinylestradiol (EES) also suppressed I(Ca,L), but testosterone and progesterone failed to inhibit I(Ca,L) The potency of the inhibitory effect on I(Ca,L) was DES> EES> 17beta-estradiol. 7. 17Beta-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 effects, possibly by acting the L-type Ca2+ channels. The antiarrhythmic effects of oestrogens may contribute to the cardioprotective actions of oestrogens.
Insights
Estrogens, particularly 17beta-estradiol, demonstrate antiarrhythmic effects by inhibiting L-type calcium channels in guinea-pig atrial myocytes. These findings suggest a role for estrogen in cardioprotection.
Area of Science:
- Cardiovascular Physiology
- Endocrinology
- Electrophysiology
Background:
- Estrogens are known to influence cardiovascular function.
- The specific electrophysiological effects of estrogens on cardiac myocytes require further elucidation.
- Understanding these mechanisms may reveal novel therapeutic targets for arrhythmias.
Purpose of the Study:
- To investigate the effects of 17beta-estradiol on action potential and membrane currents in guinea-pig atrial myocytes.
- To determine the impact of estrogen on calcium and potassium currents.
- To explore the potential antiarrhythmic mechanisms of estrogen.
Main Methods:
- Single guinea-pig atrial myocytes were utilized for electrophysiological recordings.
- Action potentials were measured under current and voltage clamp conditions.
- Voltage-dependent calcium currents (I(Ca,T) and I(Ca,L)) and potassium currents (I(K)) were analyzed.
Main Results:
- 17beta-estradiol shortened action potential duration and abolished E-4031-induced early afterdepolarizations.
- Estrogen significantly reduced L-type calcium currents (I(Ca,L)) concentration-dependently and suppressed T-type calcium currents (I(Ca,T)) slightly.
- Estrogen also inhibited cyclic AMP-enhanced I(Ca,L) and demonstrated antiarrhythmic effects on isoproterenol-induced abnormal automaticity.
Conclusions:
- Estrogens, including 17beta-estradiol, exhibit specific antiarrhythmic properties.
- The primary mechanism appears to involve the inhibition of L-type calcium channels.
- These findings support a potential cardioprotective role for estrogens through modulation of cardiac electrophysiology.