Effect of 17β‐oestradiol on contraction, Ca2+ current and intracellular free Ca2+ in guinea‐pig isolated cardiac myocytes

Abstract

The effect of 17β‐oestradiol on cardiac cell contraction, inward Ca2+ current and intracellular free Ca2+ ([free Ca2+]i) was investigated in guinea‐pig single, isolated ventricular myocytes. The changes of cell length were measured by use of a photodiode array, the voltage‐clamp experiments were performed with a switch clamp system and [free Ca2+]i was measured with the Ca2+ indicator, Fura‐2. 17β‐Oestradiol (10, 30 μm) caused a decrease in cell shortening at both 22 and 35°C. This negative inotropic effect was accompanied by a decrease in action potential duration mainly brought about by a shortening of the plateau region of the action potential. 17β‐Oestradiol (10, 30 μm) induced a similar decrease in cell shortening in voltage‐clamped and current‐clamped cells. In Fura‐2 loaded cells, 17β‐oestradiol (10 and 30 μm) decreased systolic Fura‐2 fluorescence to 72 ± 7% and 47 ± 4% (n = 6, P < 0.001) of control respectively. 17β‐Oestradiol (10 μm) had no significant effect on diastolic Fura‐2 fluorescence, but at higher concentration (30 μm) induced a slight decrease in resting Fura‐2 fluorescence. The effect of 17β‐oestradiol was reversible after 1–2 min of washout of the steroid. 17β‐Oestradiol (10 and 30 μm) decreased the peak inward Ca2+ current (ICa), which was sensitive to [Ca2+]o, dihydropyridines and isoprenaline, to 59 ± 3% and 39 ± 5% (n = 7∼9, P < 0.01) respectively, without producing any significant change in the shape of the current‐voltage relationship. The recovery time of ICa from inactivation was delayed by 17β‐oestradiol (10 μm). The inhibitory effect of 17β‐oestradiol on ICa was less at a holding potential of −80 mV than at −40mV. We conclude that 17β‐oestradiol has a negative inotropic effect on guinea‐pig single ventricular myocytes by inhibiting ICa and so reducing systolic [Ca2+]i. 17β‐Oestradiol may therefore have a Ca2+ channel blocking property in guinea‐pig isolated ventricular myocytes. 1992 British Pharmacological Society