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Oestrogen upregulates L‐type Ca 2+ channels via oestrogen‐receptor‐α by a regional genomic mechanism in female rabbit hearts
Author(s) -
Yang Xiaoyan,
Chen Guojun,
Papp Rita,
DeFranco Donald B.,
Zeng Fandian,
Salama Guy
Publication year - 2012
Publication title -
the journal of physiology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.802
H-Index - 240
eISSN - 1469-7793
pISSN - 0022-3751
DOI - 10.1113/jphysiol.2011.219501
Subject(s) - repolarization , endocrinology , medicine , calcium , estrogen , receptor , intracellular , calcium in biology , chemistry , electrophysiology , biochemistry
Non‐technical summary Women during their child‐bearing years have longer QT intervals in their electrocardiograms than men and are more susceptible to lethal arrhythmias elicited by drugs that delay repolarization. Current theories posit that women have a reduced ‘repolarization reserve’ due to reduced potassium currents resulting in longer QT and greater repolarization delays. We proposed an alternative mechanism of higher calcium currents in women which would likewise prolong QT intervals, delay repolarization while increasing the force of contractions and intracellular calcium load. Here, we show that physiological concentrations of oestrogen increase the calcium current only in cells from the base of the heart, by increasing messenger RNA and proteins levels that encode for the calcium current. Moreover, oestrogen acts by interacting with oestrogen receptors (ER)α but not ERβ which may explain why hormone replacement therapy increases the risk of arrhythmia and offers a possible protective solution of using an oestrogen mimetic that selectively binds to ERβ.