Table 2.
Effect of E2 and GPER on proteins/messengers involved in Ca2+-dependent cardiac function.
| Ca2+ signaling protein involved | Assay | Model/Intervention/Treatment | Tissue/cells examined | Effects of intervention |
|---|---|---|---|---|
| L-type Ca2+ channels (Cav1.2) | Agonist-induced Ca2+ signal | G1 (68) G1 (69) G36 (69) |
ISO-induced HFpEF myocytes (68) Male LV myocytes (69) Male LV myocytes (69) |
Restored ISO-induced Ca2+ transient amplitude (68) ↓ ISO-induced Ca2+ signals (69) ↑ ISO-induced Ca2+ signals (69) |
| Electrically stimulated Ca2+ transient | E2 (70–72) RVT (73) E2, raloxifene (71) E2/OVX (72) OVX (74) |
Ventricular myocytes (70, 71, 73) ERα−/−, ERβ−/− myocytes (71) LV apical myocytes (72) Ventricular myocytes (74) |
↓ amplitude (70, 71, 73), delay recovery from inactivation (70) ↓ cell shortening (71) ↓ amplitude (71) ↑ amplitude (72) ↓ amplitude (74) |
|
| ISO-induced cAMP Basal cAMP |
E2 (75) OVX (72) OVX/E2 or G1 (72) |
Perfused heart (75) LV apex (72) LV apex (72) |
↓ cAMP (75) ↓ cAMP (72) Restored to sham level (72) |
|
| Cav1.2 mRNA immunoblotting |
OVX (72) E2/OVX (72) |
LV apical myocytes (72) LV apical myocytes (72) |
↓ mRNA (72) Restored to sham level (72) | |
| RyR2 | Immunoblotting | G1/ OVX-HTN (25) | LV tissue (25) | No change (25) |
| Caffeine-induced SR Ca2+ release | OVX (74) | Ventricular myocytes (74) | ↑ SR Ca2+ release (74) | |
| 45Ca2+ flux | OVX (76) E2/OVX (76) PKA (-)/ OVX (76) |
LV myocytes (76) LV myocytes (76) LV myocytes (76) |
↑45Ca2+ flux (76) Restored to sham level (76) Restored to sham level (76) |
|
| SR Ca2+-ATPase (SERCA) | Agonist-induced SR Ca2+ accumulation | G1 (24) | Saponin-skinned myocytes (24) | ↑ Ca2+ accumulation (24) |
| SR Ca2+ uptake | OVX (77) E2/OVX (77) Progesterone/OVX (77) |
LV tissue (77) LV tissue (77) LV tissue (77) |
↓ uptake (77) Restored uptake (77) Restored uptake (77) |
|
| Immunoblotting | OVX (76) E2/OVX (76) G1/OVX old-aged (24) |
LV myocytes (76) LV myocytes (76) LV tissue (24) |
No change (76) No change (76) ↑ expression (24) |
|
| Phospholamban (PLB) | PLB mRNA PLB immunoblot |
G1/OVX-HTN (25) OVX/MCT-PAH (20) OVX/G1/MCT-PAH (20) |
LV tissue (25) RV tissue (20) RV tissue (20) |
No change (25) ↓pPLB/PLB expression (20) Restored normal expression (20) |
| Ser16 PLB phosphorylation | OVX (77) | LV tissue (77) | No change | |
| Thr17 PLB phosphorylation | OVX (77) E2/OVX (77) Progesterone/OVX (77) |
LV tissue (77) LV tissue (77) LV tissue (77) |
↓ Thr17 phosphorylation (77) Restored Thr17 phosphorylation (77) Restored Thr17 phosphorylation (77) |
|
| Na+/Ca2+ exchanger (NCX) | Na+-dependent Ca2+ uptake | OVX (76) E2/OVX (76) PKA(–)/OVX (76) |
LV myocytes (76) LV myocytes (76) LV myocytes (76) |
↑ Na+-dependent Ca2+ uptake (76) Restored to sham level (76) Restored to sham level (76) |
E2, estrogen; ER, estrogen receptor; HTN, hypertension; HFpEF, heart failure with preserved ejection fraction; ISO, isoproterenol; LV, left ventricular; MCT-PAH, monocrotaline-induced pulmonary arterial hypertension; OVX, ovariectomized; pPLB, phosphorylated phospholamban; PKA, protein kinase A; RV, right ventricular; RVT, right ventricular free wall thickness; RyR, ryanodine receptor; SR, sarcoplasmic reticulum.