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17β-Estradiol inhibits the voltage-dependent L-type Ca2+ currents in aortic smooth muscle cells

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Abstract

To elucidate the mechanisms of estrogens-induced relaxation effects on vascular smooth muscle cells, the effects of estrogens and the related hormones were examined in cultured rat thoracic aortic smooth muscle cell lines (A7r5), using the whole-cell voltage clamp technique. The patch pipette was filled with 140 mM CsCl- or KCl-containing internal solution. With CsCl-internal solution, 17β-estradiol and synthetic estrogens, ethynylestradiol and diethylstilbestrol (0.1–30 μM) inhibited the Ba2+ inward current (IBa) through the voltage-dependent L-type Ca2+ channel in a concentration-dependent and reversible manner. The potency of the inhibitory effects on IBa was 17β-estradiol < ethynylestradiol < diethylstilbestrol. 17β-Estradiol (10 μM) appeared to reduce the maximal conductance of IBa with only a slight shift of voltage-dependency of inactivation and to affect IBa in a use-independent fashion. On the other hand, testosterone and progesterone (30 μM) failed to affect IBa. At a holding potential of −40 mV, both vasopressin and endothelin-1 (100 nM) activated a long-lasting inward current. After endothelin-1 (100 nM) activated the current, the additional application of vasopression (100 nM) could not induce it furthermore, suggesting that each agonist activates the same population of the channels. The reversal potential of the current was about 0 mV and was not significantly altered by replacement of [Cl]i or [Cl]0 and the inward current was also observed even when extracellular cations are Ca2+, proposing that it was a Ca2+-permeable non-selective cation channel (IN.S.). La3+ or Cd2+ (1 mM) completely abolished IN.S., however, nifedipine (10 μM) failed to inhibit it at all. Diethylstilbestrol (1–30 μM) suppressed the IN.S. evoked by both endothelin-1 and vasopressin in a concentration-dependent manner, while 17β-estradiol, ethynylestradiol, progesterone and testosterone (30 μM) failed to inhibit it significantly. In addition, at a holding potential of +0 mV, 17β-estradiol by itself did not affect the holding currents, and did not inhibit K+ currents evoked by endothelin-1 or vasopressin, possibly due to the Ca2+ release from the storage sites. These results suggest that 17β-estradiol may play a role in regulating vascular tone, selectively by inhibiting the voltage-dependent L-type Ca2+ current in vascular smooth muscle cells.

Keywords

17β-Estradiol
Estrogen
Vascular smooth muscle
Ca2+ current, L-type, voltage-dependent
Endothelin-1
Vasopressin
Ca2+-permeable non-selective cation current

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