Antiarrhythmic effect and its underlying ionic mechanism of 17β‐estradiol in cardiac myocytes

Abstract

1 The eects of oestrogens on action potential and membrane currents were examined in single guinea-pig atrial myocytes. 2 17b-estradiol (3 ± 10 mM) shortened the action potential duration without signi®cant changes in the resting membrane potential. E-4031 (1 mM) markedly prolonged the action potential duration and induced early afterdepolarization, and 17b-estradiol (10 mM) 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 17b-estradiol. 4 Under voltage clamp conditions, the voltage-dependent Ca 2+ currents consisted of both T-(I Ca.T ) and L-type (I Ca.L ). 17b-estradiol reduced I Ca.L concentration-dependently, while it (10 mM) suppressed I Ca.T only by approximately 10%. 17b-estradiol did not aect time courses of I Ca.L inactivation, but it shifted the steady-state inactivation curve to more negative potentials. 5 17b-estradiol (10 mM) did not aect the time-dependent K + current (I K ), referred to as I Kr and I Ks , and inwardly rectifying K + current. However, 17b-estradiol (30 mM) or diethylstilbestrol (10 mM) 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 eect on I Ca.L was DES4EES417b-estradiol. 7 17b-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 eects of oestrogen on I Ca.L . 8 These results suggest that oestrogen speci®cally has antiarrhythmic eects, possibly by acting the L-type Ca 2+ channels. The antiarrhythmic eects of oestrogens may contribute to the cardioprotective actions of oestrogens.

Raloxifene acutely suppresses ventricular myocyte contractility through inhibition of the L‐type calcium current

“…The profound inhibition of I Ca,L by raloxifene over the range of potentials tested is similar to previously documented direct actions of 17b-oestradiol on cardiac myocytes (Jiang et al, 1992;Grohe et al, 1996;Nakajima et al, 1999a). However, raloxifene did not significantly shift the steady-state activation or inactivation curves.…”

Differential Effects of Sarcolemmal and Mitochondrial KATP Channels Activated by 17β-Estradiol on Reperfusion Arrhythmias and Infarct Sizes in Canine Hearts

“…However, a Kir blocker terikalant has no effect on the current of ATP-sensitive K ϩ channel (Escande, 1989). Thus, it is not surprising that although 17␤-estradiol did not exert any effect on Kir channels (Nakajima et al, 1999;Tanabe et al, 1999), it can activate ATP-sensitive K ϩ channels. Many agonists have been shown to trigger the opening of ATP-sensitive K ϩ channels, including adenosine, bradykinin, opioids, and free radicals (Downey and Cohen, 1997).…”

“…17␤-Estradiol has been shown to activate K ϩ channels in some (Sudhir et al, 1995;Hugel et al, 1999) but not all studies (Nakajima et al, 1999;Tanabe et al, 1999). The ATP-sensitive K ϩ channel, a member of the superfamily of Kir channels, is a heteromultimer composed of a pore-forming K ϩ channel core and a regulating ATP-binding cassette protein (Jovanovic et al, 1999).…”

Regulation of the sperm calcium channel CatSper by endogenous steroids and plant triterpenoids

“…The female hormone progesterone (P4) activates the principal calcium channel of sperm (CatSper) (2)(3)(4)(5) and blocks the potassium channel KSper (6) via these nongenomic pathways (7). The modulation of ion channel functions by steroid hormones has been reported in the heart (8,9), neurons (10)(11)(12), smooth muscle (13), and pancreatic beta cells (14). In marine invertebrates, the sulfated steroid cholestane acts as a chemoattractant for sea squirt sperm, which also happens via the nongenomic pathway (15).…”