Oestrogen directly inhibits the cardiovascular L-type Ca2+ channel Cav1.2.
Oestrogen can modify the contractile function of vascular smooth muscle and cardiomyocytes. The negative inotropic actions of oestrogen on the heart and coronary vasculature appear to be mediated by L-type Ca(2+) channel (Ca(v)1.2) inhibition, but the underlying mechanisms remain elusive. We tested the hypothesis that oestrogen directly inhibits the cardiovascular L-type Ca(2+) current, I(CaL). The effect of oestrogen on I(CaL) was measured in Ca(v)1.2-transfected HEK-293 cells using the whole-cell patch-clamp technique. The current revealed typical activation and inactivation profiles of nifedipine- and cadmium-sensitive I(CaL). Oestrogen (50 microM) rapidly reduced I(CaL) by 50% and shifted voltage-dependent activation and availability to more negative potentials. Furthermore, oestrogen blocked the Ca(2+) channel in a rate-dependent way, exhibiting higher efficiency of block at higher stimulation frequencies. Our data suggest that oestrogen inhibits I(CaL) through direct interaction of the steroid with the channel protein.
Ullrich
Nina D
ND
Imperial College London, Cardiac Medicine, NHLI London, UK. ullrich@pyl.unibe.ch
Koschak
Alexandra
A
MacLeod
Kenneth T
KT
D019256:Cadmium Chloride / Q000494:pharmacology; D020746:Calcium Channels, L-Type / Q000378:metabolism*; D002319:Cardiovascular System / Q000187:drug effects / Q000378:metabolism*; D002460:Cell Line; D004958:Estradiol / Q000494:pharmacology; D004967:Estrogens / Q000494:pharmacology*; D006801:Humans; D015640:Ion Channel Gating / Q000187:drug effects*; D009543:Nifedipine / Q000494:pharmacology; D014162:Transfection
D020746:Calcium Channels, L-Type; D004967:Estrogens; C419385:L-type calcium channel alpha(1C); D004958:Estradiol; D009543:Nifedipine; D019256:Cadmium Chloride