HOME HELP FEEDBACK SUBSCRIPTIONS ARCHIVE SEARCH TABLE OF CONTENTS		QUICK SEARCH:   [advanced] Author: Keyword(s): Year:  Vol:  Page:

This Article Full Text Full Text (PDF) All Versions of this Article: 294/6/H2421    most recent 01225.2007v1 Alert me when this article is cited Alert me if a correction is posted Citation Map Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Citing Articles Citing Articles via Google Scholar Google Scholar Articles by Ullrich, N. D. Articles by MacLeod, K. T. Search for Related Content PubMed PubMed Citation Articles by Ullrich, N. D. Articles by MacLeod, K. T.

CALL FOR PAPERS
Sex Steroids and Gender in Cardiovascular-Renal Physiology and Pathophysiology

Genomic deletion of estrogen receptors ER and ERβ does not alter estrogen-mediated inhibition of Ca²⁺ influx and contraction in murine cardiomyocytes

¹Imperial College London, Cardiac Medicine, National Heart and Lung Institute, London, United Kingdom; and ²Université Louis Pasteur, Institut de Génétique et Biologie Moléculaire et Cellulaire, Centre National de la Recherche Scientifique, Illkirch, Communauté Urbaine de Strasbourg, France

Submitted 22 October 2007 ; accepted in final form 21 April 2008

Estrogens modify contraction of vascular smooth muscle and cardiomyocytes, but suggestions that they confer protective effects on the cardiovascular system remain controversial. The negative inotropic effects of estrogens are a consequence of L-type Ca²⁺ channel inhibition, but the underlying mechanisms remain elusive. We tested the hypothesis that membrane-associated estrogen receptors (ER)- and -β are involved. We measured the effect of estrogens on Ca²⁺ current (I_CaL) in isolated ventricular cardiomyocytes of wild-type (WT), ER knockout (ERKO), and ERβKO mice using the whole cell patch-clamp technique at 37°C. No differences in current densities or inactivation profiles of I_CaL were found under control conditions in WT, ERKO, and ERβKO cardiomyocytes, suggesting that absence of either ER has no effect on functional properties of I_CaL. In all groups, application of raloxifene (2 µM) or 17- or 17β-estradiol (50 µM) reduced I_CaL (P < 0.001). Raloxifene decreased I_CaL by 44 ± 9% (mean ± SE) in WT (n = 5), 34 ± 5% in ERKO (n = 5), and 30 ± 5% in ERβKO mice (n = 8). 17-Estradiol reduced I_CaL by 41 ± 10% in WT (n = 4), 34 ± 12% in ERKO (n = 7), and 38 ± 8% in ERβKO mice (n = 7). 17β-Estradiol inhibited I_CaL by 31 ± 4% in WT (n = 4), 28 ± 6% in ERKO (n = 3), and 42 ± 3% in ERβKO mice (n = 5). Decreases in cell shortening occurred in parallel with these findings. Our results suggest that inhibition of I_CaL and the decrease in contraction by estrogens do not depend on ER or ERβ.

L-type calcium channel; excitation-contraction coupling; cardiac electrophysiology