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

Abstract

4 17P-Oestradiol (10 and 30 SM) decreased the peak inward Ca2+ current (ICa), which was sensitive to [Ca2+]0, 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 17p-oestradiol (10 tiM). The inhibitory effect of 17p-oestradiol on ICa was less at a holding potential of -80 mV than at -40 mV.

Raloxifene acutely suppresses ventricular myocyte contractility through inhibition of the L‐type calcium current

“…The profound inhibition of I Ca,L by raloxifene over the range of potentials tested is similar to previously documented direct actions of 17b-oestradiol on cardiac myocytes (Jiang et al, 1992;Grohe et al, 1996;Nakajima et al, 1999a). However, raloxifene did not significantly shift the steady-state activation or inactivation curves.…”

“…Similar experiments on field stimulated myocytes were performed with 17b-oestradiol in order to compare the acute actions of the two oestrogenic compounds. As the acute cardiac actions of 17b-oestradiol have previously been demonstrated to occur at supra-physiological concentrations (Jiang et al, 1992;Meyer et al, 1998), we chose to use a concentration of 40 mM in these experiments. Both raloxifene and 17b-oestradiol significantly decreased cell shortening and the Dindo-1 ratio (Figure 2).…”

“…It has long been known that 17b-oestradiol can exert direct actions on the heart through inhibition of the L-type calcium current (I Ca,L ), although these effects have tended to occur at supra-physiological concentrations (Jiang et al, 1992;Meyer et al, 1998). In the present study, we tested the hypothesis that raloxifene acts as a Ca 2 þ channel antagonist on the heart and suppresses ventricular myocyte contractility in a similar way to 17b-oestradiol.…”

Greater antiarrhythmic activity of acute 17β‐estradiol in female than male anaesthetized rats: correlation with Ca2+ channel blockade

“…Only one concentration of drug or vehicle was tested per cell and myocytes from at least three rats were used to acquire data for each drug concentration. Concentrations of 10 and 30 mM were examined first, as these had been reported to be effective previously in guinea-pig myocytes (Jiang et al, 1992) then further concentrations were examined to explore the full concentration-response relationship.…”

“…In previous work on the action of 17b-estradiol on I CaL in cardiac myocytes, only cells from male guinea pigs were studied (Jiang et al, 1992) or the inhibition of the current was reported to be independent of sex (Meyer et al, 1998). However, Ca 2 þ entry into vascular smooth muscle cells was inhibited by 17b-estradiol to a much greater extent in cells from female rats than in those from male rats (Crews and Khalil, 1999).…”