Objectives: Reports of testosterone effects on cardiovascular morbidity remain contradictory. Besides modulating cardiovascular risk factors recent evidence indicates direct actions of testosterone on cardiac tissue. However, the impact on human cardiac L-type calcium channels that play a central role in electro-mechanical coupling is unknown.
Methods and results: Human ventricular myocytes were isolated from patients undergoing heart transplantation. Patch-clamp experiments in whole-cell configuration were performed to evaluate the effect of dihydrotestosterone on cardiac L-type calcium current I(Ca,L). Treatment of cultured cardiomyocytes with dihydrotestosterone 100 nmol/L for 24-30 h increased the whole-cell I(Ca,L) current density from 2.32 +/- 0.17 pA/pF (n = 11) to 3.21 +/- 0.17 pA/pF (n = 14) at +10 mV (p = 0.01) without shifting the current-voltage relation. This effect was associated with a 1.35-fold higher expression of the pore-forming Ca(V)1.2 (alpha1c) subunit of L-type calcium channels in dihydrotestosterone-treated myocytes compared with controls (p = 0.03).
Conclusions: Dihydrotestosterone treatment increased L-type calcium current density by the upregulation of Ca(V)1.2 in human ventricular myocytes. These data provide a possible explanation for dihydrotestosterone effects on the cardiovascular system in androgenic steroid abuse.