Rapid modulation of L-type calcium current by acutely applied oestrogens in isolated cardiac myocytes from human, guinea-pig and rat

被引:75
作者
Meyer, R [1 ]
Linz, KW
Surges, R
Meinardus, S
Vees, J
Hoffmann, A
Windholz, O
Grohé, C
机构
[1] Univ Bonn, Inst Physiol, Bonn, Germany
[2] Univ Bonn, Med Poliklin, Bonn, Germany
关键词
D O I
10.1113/expphysiol.1998.sp004115
中图分类号
Q4 [生理学];
学科分类号
071003 ;
摘要
Gender-based differences in cardiovascular mortality may be due to a cardio-protective effect of oestrogens on the myocardium. However, mRNA expression of oestrogen receptors in myocardial tissue of the adult heart has yet to be demonstrated. Furthermore, a calcium antagonistic action of 17 beta-oestradiol on myocardial tissue has been discussed. Therefore, two subjects were investigated in atrial myocytes of the human, and ventricular myocytes of guinea-pig and rat in this study. (1) Are oestrogen receptors expressed in adult myocardial cells? (2) Is there an influence of oestrogens on the L-type calcium current of cardiac myocytes? Expression of oestrogen receptors was investigated by reverse polymerase chain reaction. L-type calcium current was usually measured by the patch-clamp technique in whole-cell recording mode under selective recording conditions, i.e. overlapping currents were blocked. One series of experiments was performed in perforated patch configuration to avoid internal perfusion. 17 beta-Oestradiol inhibited L-type calcium current reversibly in all three species. At 10(-5) M, the inhibition was 15-20%. This inhibition was independent of the sex and the species. A full concentration-response curve of 17 beta-oestradiol on basal L-type current was recorded from female guinea-pig myocytes. The inhibition increased from 2 % at 10(-7) M to about 30 % at 10(-4) M 17 beta-oestradiol. The values could be fitted by a sum of two sigmoidal functions with log EC50 values of -6.5 and -4.9 M and Hill slopes of 2.5 for both. The specificity of the 17 beta-oestradiol action was tested by recording the L-type current in the presence of 17 alpha-oestradiol and oestrone. 17 alpha-Oestradiol also inhibited the current, but with a maximal inhibition of only 17 %. The concentration-response curve could be fitted by a single sigmoidal function (log EC50 -6.3 M; Hill slope 0.55). Oestrone did not influence the current at all. The decrease in L-type current after the application of 17 beta-oestradiol via a rapid perfusion system developed with a time constant of 3.4 s, which was in the same range as that for the influence of isoprenaline. The isoprenaline-stimulated L-type current was much more susceptible to the inhibition by 17 beta-oestradiol, i.e., in pre-stimulated cells (1) the inhibitory effect is significantly higher (e.g. at 10(-5) M, inhibition was 36.3 % compared with 11.2 % in untreated cells) and (2) an inhibitory effect can be seen with oestradiol concentrations as low as 10(-9) M. Although the concentrations needed to gain a calcium antagonistic influence on the basal current were much too high to explain a cardio-protective influence of oestrogens, the presence of oestrogen receptors in cardiac myocytes of all three species, together with the shift in concentration dependence following pre-stimulation by isoprenaline, suggest that myocytes are a potential target for oestrogen.
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页码:305 / 321
页数:17
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