Effects of 17beta-estradiol on action potentials and ionic currents in male rat ventricular myocytes.

Abstract

This study describes electrophysiological effects of estrogens in isolated male rat ventricular myocytes. According to the literature these cells do not express the nuclear estrogen receptor. Action potentials or membrane currents were recorded in the whole-cell configuration with standard techniques. Action potential durations (APD) measured at a level of 0 mV (APD 0) and -70 mV (APD -70) were prolonged by 17beta-estradiol (0.5 Hz stimulation frequency, 24-26 degrees C). Threshold concentration was 1 micromol/l. At the highest concentration used (30 micromol/l) no saturation of the response was reached and APD 0 was 162% and APD -70 was 230% of the respective control. The resting potential remained unaffected in most cells. The prolongation induced by 17beta-estradiol developed fast and reached a steady state 10 min after start of hormone superfusion. Effects of estrogen were completely reversible during 10-15 min wash-out with hormone-free solution. The extent of prolongation (10 micromol/l 17beta-estradiol) was frequency dependent. Expressed as percentage of the respective control APD 0 (or APD -70) was 115% (188%) at 0.05 Hz, 118% (163%) at 0.5 Hz and 99% (129%) at 5 Hz stimulation frequency. The response was stereoselective, because 30 micromol/l 17alpha-estradiol did not prolong action potentials (APD 0: 101%, APD -70: 104% of the respective control, 0.5 Hz stimulation frequency). The endogenous estrogens estrone and estriol were less effective than 17beta-estradiol. With 30 micromol/l estrone (0.5 Hz stimulation frequency) APD 0 was 103% and ADP-70 148% of control and with 30 micromol/l estriol APD 0 was 135% and APD -70 137% of control. The prolongation of action potentials can be explained by inhibition of transient outward current which, in rat ventricle, is composed of fast (i[to,f]) and slowly (i[to,s]) inactivating components. At 30 micromol/l 17beta-estradiol i(to,f) was reduced to 50% and i(to,s) to 43% of their maximal amplitudes. The voltage sensor of i(to,f) or i(to,s) was hardly affected. Additionally, 17beta-estradiol decreased the calcium current (i[Ca,L]) to 76% (10 micromol/l) and 38% at 30 micromol/l. The inwardly rectifying potassium current (i[K1]) was reduced partly with 30 micromol/l 17beta-estradiol and its amplitude was 72% of control at -90 mV (inward current flow) and 65% at -40 mV (outward current flow). These results show that 17beta-estradiol is active in cardiac cells which do not express the nuclear estrogen receptor. The hormone exerts class III activity and reduces calcium inward current. These effects, however, occur in vitro with concentrations above the physiological level and therefore may be without significance in vivo.