EFFECT OF 17-BETA-ESTRADIOL ON CONTRACTION, CA-2+ CURRENT AND INTRACELLULAR FREE CA-2+ IN GUINEA-PIG ISOLATED CARDIAC MYOCYTES

1 The effect of 17-beta-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 17-beta-Oestradiol (10, 30-mu-M) caused a decrease in cell shortening at both 22 and 35-degrees-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. 17-beta-Oestradiol (10, 30-mu-M) induced a similar decrease in cell shortening in voltage-clamped and current-clamped cells. 3 In Fura-2 loaded cells, 17-beta-oestradiol (10 and 30-mu-M) decreased systolic Fura-2 fluorescence to 72 +/- 7% and 47 +/- 4% (n = 6, P < 0.001) of control respectively. 17-beta-Oestradiol (10-mu-M) had no significant effect on diastolic Fura-2 fluorescence, but at higher concentration (30-mu-M) induced a slight decrease in resting Fura-2 fluorescence. The effect of 17-beta-oestradiol was reversible after 1 -2 min of washout of the steroid. 4 17-beta-Oestradiol (10 and 30-mu-M) decreased the peak inward Ca2+ current (I(Ca)), which was sensitive to [Ca2+]o, dihydropyridines and isoprenaline, to 59 +/- 3% and 39 +/- 5% (n = 7 approximately 9, P < 0.01) respectively, without producing any significant change in the shape of the current-voltage relationship. 5 The recovery time of I(Ca) from inactivation was delayed by 17-beta-oestradiol (10-mu-M). The inhibitory effect of 17-beta-oestradiol on I(Ca) was less at a holding potential of -80 mV than at -40 mV. 6 We conclude that 17-beta-oestradiol has a negative inotropic effect on guinea-pig single ventricular myocytes by inhibiting I(Ca) and so reducing systolic [Ca2+]i. 17-beta-Oestradiol may therefore have a Ca2+ channel blocking property in guinea-pig isolated ventricular myocytes.