Interaction of gonadal steroids and the glucocorticoid corticosterone in the regulation of the L-type Ca2+ current in rat left ventricular cardiomyocytes

Aim: Gonadal steroids as well as glucocorticoids have been shown to regulate the cardiac L-type Ca2+ current (I-CaL). Herein, we compare the effects of the gonadal steroids testosterone and 17 beta-estradiol with the glucocorticoid corticosterone on I-CaL, and investigate the interaction between the gonadal steroids and corticosterone. Methods: Myocytes were isolated from the left ventricular free wall of female and male Wistar rats and investigated using the ruptured-patch whole-cell patch-clamp technique. Results: In myocytes isolated from female rats, 24 h incubation with 100 nm testosterone led to a 33% increase in I-CaL compared with control (-8.8 +/- 0.5 pA pF(-1), n = 25 vs. -6.6 +/- 0.4 pA pF(-1), n = 26, P < 0.01, V-Pip = 0 mV). Incubation with 1 mu m corticosterone resulted in a 79% increase in I-CaL (-11.8 +/- 0.7 pA pF(-1), n = 29, P < 0.001). However, the combination of testosterone and corticosterone did not have any additional effect compared with corticosterone alone (-11.7 +/- 0.6 pA pF(-1), n = 25, ns). In cardiomyocytes from male rats, I-CaL was not affected by testosterone, whereas the effect of corticosterone was preserved (P < 0.05). 24 h incubation with 17 beta-estradiol increased I-CaL by 32% from) 7.6 +/- 0.5 pA pF(-1) (n = 15) to 10.0 +/- 0.9 pA pF(-1) (n = 15, P < 0.05). 17 beta-estradiol did not exert an additional effect upon co-incubation with corticosterone and did not have an effect on I-CaL in cardiomyocytes from female rats. Higher concentrations of the gonadal steroids did not result in increased effects. Conclusion: When compared with corticosterone, the in vitro effects of the gonadal steroids are small. However, under conditions in which I-CaL is not fully activated by glucocorticoids, gonadal steroids may significantly contribute to I-CaL regulation.