抄録
[Aim] We investigated acute effects of sex hormone on membrane currents of cardiomyocytes, and their intracellular signal transduction mechanism. [Methods] Cardiac membrane currents were recorded with amphotericin B-induced perforated patch from guinea-pg ventricular myocytes. Intracellular signal transduction mechanism was investigated by Western blot analysis and immunoprecipitation. [Results] (1) Both 17β-estradiol (E2) and 17β-dihydrotestosterone (DHT) enhanced slowly-activating delayed rectifier K+ current (IKs) in a concentration-dependent manner with an IC50 of 10.3±0.2 nM and 1.1±0.1 nM, respectively. IKs enhancement by E2 and DHT was inhibited by a blocker of estrogen receptor (ER), ICI182780, and androgen receptor (AR), nilutamide, respectively. (2) IKs enhancement by E2 and DHT was inhibited by NOS3 inhibitor, but not by NOS1 inhibitor. NOS3 is activated by either Ca2+/calmodulin(CaM)- or Ser/Thr kinase, Akt-dependent manner. IKs enhancement by E2 and DHT was inhibited by Akt inhibitor, but not by CaM inhibitor, W7. (3) E2 and DHT induced phosphorylation of Akt and NOS3. NOS3 phosphorylation was inhibited by Src inhibitor (PP2), PI3 kinase inhibitor (wortmannin), Akt inhibitor, and hsp90 inhibitor (geldanamycin). Akt phosphorylation was inhibited by PP2 and wortmannin, but not by Akt inhibitor or geldanamycin. [Conclusion] E2 and DHT enhanced IKs by NO produced through non-genomic pathway of E2 and DHT. [Jpn J Physiol 54 Suppl:S125 (2004)]
