Oestrogen directly inhibits the cardiovascular L-type Ca{sup 2+} channel Ca{sub v}1.2
- Imperial College London, Cardiac Medicine, NHLI London (United Kingdom) and University of Bern, Department of Physiology, Buehlplatz 5, CH-3012 Bern (Switzerland)
- University of Innsbruck, Department of Pharmacology and Toxicology, Innsbruck (Austria)
- Imperial College London, Cardiac Medicine, NHLI London (United Kingdom)
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{sup 2+} channel (Ca{sub v}1.2) inhibition, but the underlying mechanisms remain elusive. We tested the hypothesis that oestrogen directly inhibits the cardiovascular L-type Ca{sup 2+} current, I {sub CaL}. The effect of oestrogen on I {sub CaL} was measured in Ca{sub 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 {sub CaL}. Oestrogen (50 {mu}M) rapidly reduced I {sub CaL} by 50% and shifted voltage-dependent activation and availability to more negative potentials. Furthermore, oestrogen blocked the Ca{sup 2+} channel in a rate-dependent way, exhibiting higher efficiency of block at higher stimulation frequencies. Our data suggest that oestrogen inhibits I {sub CaL} through direct interaction of the steroid with the channel protein.
- OSTI ID:
- 20991550
- Journal Information:
- Biochemical and Biophysical Research Communications, Vol. 361, Issue 2; Other Information: DOI: 10.1016/j.bbrc.2007.07.054; PII: S0006-291X(07)01538-0; Copyright (c) 2007 Elsevier Science B.V., Amsterdam, The Netherlands, All rights reserved; Country of input: International Atomic Energy Agency (IAEA); ISSN 0006-291X
- Country of Publication:
- United States
- Language:
- English
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