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Activation of the ERα and ERβ pathway downregulates voltage‐gated Ca 2+ channels in coronary arteries
Author(s) -
Gray William R.,
Dalton Robin J.,
Sketas Greg,
Hill Brent J.F.
Publication year - 2012
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.26.1_supplement.863.4
Subject(s) - gper , downregulation and upregulation , coronary arteries , western blot , antagonist , endocrinology , estrogen receptor , medicine , estrogen , voltage dependent calcium channel , chemistry , receptor , calcium , artery , biochemistry , cancer , breast cancer , gene
Our lab has previously demonstrated that a physiological concentration (1 nM) of estrogen (E2) can downregulate voltage‐gated, L‐type Ca 2+ (VGCC) channels in coronary arteries. The distal ends of coronary arteries obtained from hearts of female pigs were sectioned into longitudinal strips and incubated for 24 hrs in 1 nM E2, EtOH, an estrogen receptor (ER) α/β antagonist (ICI 182,780), and a G protein‐coupled ER antagonist (GPER; G15). The arterial strips were homogenized for Western blot analysis using an antibody reactive to the VGCC alpha 1C subunit and protein kinase Gα. Our preliminary results suggest that the E2 induced VGCC downregulation is mediated through ER α/β, and not GPER. Furthermore, ER activation by E2 in endothelium intact arteries have an increase in PKG expression (known to inhibit VGCCs), decrease in VGCC expression, and less coronary arterial reactivity. Overall, our results suggest that the classical ERs can be therapeutically targeted in women to reduce the density of VGCCs. Support: NCRR of the NIH, Grant #P20 RR‐16460 and the Arkansas SURF program.