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The sarcoplasmic reticulum enhances voltage‐gated Ca 2+ influx in resistance arteries from ovariectomized mice (680.19)
Author(s) -
Hill Brent,
Fernando Charmain
Publication year - 2014
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.28.1_supplement.680.19
Subject(s) - ovariectomized rat , endocrinology , medicine , thapsigargin , ryanodine receptor , endoplasmic reticulum , chemistry , fura 2 , agonist , mesenteric arteries , calcium , estrogen , receptor , artery , enzyme , cytosol , biochemistry
Estrogen attenuates Ca2+ entry into arterial smooth muscle cells via its inhibition and/or downregulation of voltage‐gated Ca2+ channels (VGCCs). The purpose of this study is to determine the effect of the sarcoplasmic reticulum (SR) on VGCC function in ovariectomized (OVX) mice. Female mice (C57BL/6) underwent an ovariectomy or sham (SHAM) surgery at 8 wks of age. At 12 wks of age the mice were sacrificed. Compared to SHAM mice, the OVX mice had a 50% decrease in plasma E2 and a 7‐fold reduction in uteri weight. Smooth muscle cells were isolated from the mesenteric arteries and loaded with the ratiometric calcium indicator, fura‐2AM, to conduct fluorescent imaging on these cells. There was an enhanced fura‐2 ratio in cells from OVX mice exposed to the selective VGCC agonist, FPL64176 (1x10‐6 M; p=0.03). However, when the SR was Ca2+ depleted (using the ryanodine receptor agonist, caffeine, and the SR Ca2+‐ATPase pump inhibitor, thapsigargin) before exposing the cells to FPL64176 there was no difference (p=0.40) in the fura‐2 ratio between OVX and SHAM mice. These data suggest that the SR enhances the VGCC‐mediated entry of Ca2+ into smooth muscle cells in mice with low circulating plasma E2 levels. Overall, the decline of circulating estrogen in women can enhance Ca2+ entry into arterial cells. Long‐term this may lead to an elevation in arterial tone in resistance arteries. Grant Funding Source : Supported by NIGMM of the NIH, Grant #P20 GM103429‐11