Estradiol up-regulates L-type Ca<sup>2+</sup> channels via membrane-bound estrogen receptor / Phosphoinositide-3kinase / Akt / cAMP response element-binding protein signaling pathway.
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| Abstract | :  In long QT type-2 (LQT2), women are more prone to lethal arrhythmias called Torsade de Pointes (TdP) than men. We previously reported that 17-β-estradiol (E2) upregulates L-type Ca2+-channels and current (ICa,L) (∼30%) in rabbit ventricular myocytes by a classical genomic-mechanism mediated by estrogen-receptor-α (ER)α. In LQT2 ( IKr-blockade or bradycardia), the higher Ca2+ influx via ICa,L, causes Ca2+-overload, spontaneous sarcoplasmic reticulum Ca2+-release, and re-activation of ICa,L that trigger early afterdepolarizations (EADs) and TdP. | 
| Year of Publication | :  2018 | 
| Journal | :  Heart rhythm | 
| Date Published | :  2018 | 
| ISSN Number | :  1547-5271 | 
| URL | :  http://linkinghub.elsevier.com/retrieve/pii/S1547-5271(18)30019-5 | 
| DOI | :  10.1016/j.hrthm.2018.01.019 | 
| Short Title | :  Heart Rhythm | 
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