title: Dehydroepiandrosterone (DHEA) inhibits voltage-gated T-type calcium channels.
abstract: OBJECTIVE
  Dehydroepiandrosterone (DHEA) and its sulfated form, DHEAS, are the most abundant steroid hormones in the mammalian blood flow. DHEA may have beneficial effects in various pathophysiological conditions such as cardiovascular diseases or deterioration of the sense of well-being. However to date, the cellular mechanism underlying DHEA action remains elusive and may involve ion channel modulation. In this study, we have characterized the effect of DHEA on T-type voltage-activated calcium channels (T-channels), which are involved in several cardiovascular and neuronal diseases.
  
  
  RESULTS
  Using the whole-cell patch-clamp technique, we demonstrate that DHEA inhibits the three recombinant T-channels (Ca(V)3.1, Ca(V)3.2 and Ca(V)3.3) expressed in NG108-15 cell line, as well as native T-channels in pulmonary artery smooth muscle cells. This effect of DHEA is both concentration (IC(50) between 2 and 7μM) and voltage-dependent and results in a significant shift of the steady-state inactivation curves toward hyperpolarized potentials. Consequently, DHEA reduces window T-current and inhibits membrane potential oscillations induced by Ca(V)3 channels. DHEA inhibition is not dependent on the activation of nuclear androgen or estrogen receptors and implicates a PTX-sensitive Gi protein pathway. Functionally, DHEA and the T-type inhibitor NNC 55-0396 inhibited KCl-induced contraction of pulmonary artery rings and their effect was not cumulative.
  
  
  CONCLUSIONS
  Altogether, the present data demonstrate that DHEA inhibits T-channels by a Gi protein dependent pathway. DHEA-induced alteration in T-channel activity could thus account for its therapeutic action and/or physiological effects.
authors.affiliation: Univ. Bordeaux, Centre de recherche Cardio-Thoracique de Bordeaux, Bordeaux, France.
authors.forename: M
authors.initials: M
authors.lastname: Chevalier
authors.forename: G
authors.initials: G
authors.lastname: Gilbert
authors.forename: P
authors.initials: P
authors.lastname: Lory
authors.forename: R
authors.initials: R
authors.lastname: Marthan
authors.forename: J F
authors.initials: JF
authors.lastname: Quignard
authors.forename: J P
authors.initials: JP
authors.lastname: Savineau
mesh_terms: D000818:Animals; D020747:Calcium Channels, T-Type / Q000145:classification / Q000502:physiology*; D045744:Cell Line, Tumor; D003687:Dehydroepiandrosterone / Q000494:pharmacology*; D055724:Electrophysiological Phenomena; D015640:Ion Channel Gating / Q000187:drug effects*; D051379:Mice; D009131:Muscle, Smooth, Vascular / Q000166:cytology; D032389:Myocytes, Smooth Muscle / Q000187:drug effects / Q000378:metabolism; D011651:Pulmonary Artery / Q000187:drug effects; D051381:Rats; D014664:Vasodilation / Q000187:drug effects
chemical_list: D020747:Calcium Channels, T-Type; D003687:Dehydroepiandrosterone