Impact of dihydrotestosterone on L-type calcium channels in human ventricular cardiomyocytes.
OBJECTIVE
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.


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.
Er
Fikret
F
Department of Internal Medicine III, University of Cologne, 50937 Cologne, Germany.
Gassanov
Natig
N
Brandt
Mathias C
MC
Madershahian
Navid
N
Hoppe
Uta C
UC
D000368:Aged; D002118:Calcium / Q000378:metabolism; D020746:Calcium Channels, L-Type / Q000187:drug effects* / Q000502:physiology; D002478:Cells, Cultured; D013196:Dihydrotestosterone / Q000494:pharmacology*; D005260:Female; D016027:Heart Transplantation; D006801:Humans; D008297:Male; D032383:Myocytes, Cardiac / Q000187:drug effects*; D018408:Patch-Clamp Techniques
D020746:Calcium Channels, L-Type; D013196:Dihydrotestosterone; D002118:Calcium