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

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Abstract
1 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. 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. 3 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. 4 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. 5 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. 6 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.