Regulation of beta adrenoceptor-mediated myocardial contraction and calcium dynamics by the G protein-coupled estrogen receptor 1

Abstract

The G protein‐coupled estrogen receptor (GPER) participates in many cardioprotective activities. However, the mechanisms of such activities are not known. We have begun to investigate the effects of alterations in GPER activity on myocardial signaling via the beta‐1 adrenergic receptor. In freshly isolated primary murine cardiomyocytes, β1AR agonist isoproterenol triggers robust Ca2+ signals that are oscillatory and dependent on extracellular entry. GPER activation dose‐dependently inhibits the isoproterenol‐induced Ca2+ signals. On the other hand, GPER antagonism exerts the opposite effects. Similar effects were observed in H9C2 cardiomyocytes. Mechanisms of these observations were examined on various components of myocardial Ca2+ signaling. The data indicate that GPER activity is involved in β1AR‐mediated Ca2+ signaling in the myocardium. Support or Funding Information AHA grant 15SDG25090279 (to E Wauson) and NIH Grant HL112184 (to Q‐K Tran) This abstract is from the Experimental Biology 2018 Meeting. There is no full text article associated with this abstract published in The FASEB Journal.

Estrogen Receptors: Therapeutic Perspectives for the Treatment of Cardiac Dysfunction after Myocardial Infarction

“…The reduction in cardiomyocyte apoptosis could probably be related to the activation of the PI3K/Akt pathway, as already shown for serum-deprived hypoxic CF incubated with G-1 [ 59 ]. Complementing the beneficial cardiac action of this receptor, GPER activation also regulates myocardial Ca 2+ dynamics, left ventricular pressure, and the frequency of ectopic contractions in isoproterenol-induced MI model in female rats and prevents potentiation of peak currents through L-type Ca 2+ channels in cardiomyocytes [ 95 ].…”

Reciprocality Between Estrogen Biology and Calcium Signaling in the Cardiovascular System

“…As for prevention of β adrenoceptor (βAR)-mediated potentiation of VDCE, recent evidence suggests that GPER may be an intrinsic component of β 1 AR activation. Thus, G-1 inhibits isoproterenol-induced increases in left ventricle (LV) pressure, heart rate, ectopic contractions, I Ca,L , LTCC phosphorylation, and total myocardial Ca 2+ signal, while the GPER inhibitor G-36 promotes ISO-induced Ca 2+ signal and LTCC phosphorylation ( 213 ). Speculatively, GPER may do so in part by interacting with β 1 AR or with A kinase-anchoring protein 5, thus inhibiting cAMP production ( 167 ).…”

“…Reciprocality between estrogen signaling and Ca 2+ -dependent activities is becoming evident. Considering the impact of estrogen and its receptors on Ca 2+ signaling , E 2 , and in many cases, GPER exert inhibitory effects on many components of the CSM in cardiovascular tissues, from Ca 2+ store release and uptake ( 214 , 215 , 221 ) and Ca 2+ entry ( 199 , 201 – 210 , 212 , 213 ) to cytosolic Ca 2+ removal mechanisms ( 135 , 170 , 208 , 217 – 221 ). Considering the impact of Ca 2+ signaling on estrogen biology , both ERα and GPER are strongly regulated by direct Ca 2+ -dependent interactions with CaM.…”

Role of β-Adrenergic Receptors and Estrogen in Cardiac Repair after Myocardial Infarction: An Overview

“…Numerous studies have, in fact, shown that estrogens were able to increase calcium-regulated proteins [78,79], including ATPase and membrane channels in different cell types [80][81][82][83][84]. Therefore, ERs-mediated signaling can have profound implications in the regulation of cardiac contractile activity, physiologically under the control of ARs [85][86][87].…”