2013年5月
Facilitated Hyperpolarization Signaling in Vascular Smooth Muscle-overexpressing TRIC-A Channels
JOURNAL OF BIOLOGICAL CHEMISTRY
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- 巻
- 288
- 号
- 22
- 開始ページ
- 15581
- 終了ページ
- 15589
- 記述言語
- 英語
- 掲載種別
- 研究論文(学術雑誌)
- DOI
- 10.1074/jbc.M112.435396
- 出版者・発行元
- AMER SOC BIOCHEMISTRY MOLECULAR BIOLOGY INC
The TRIC channel subtypes, namely TRIC-A and TRIC-B, are intracellular monovalent cation-specific channels and likely mediate counterion movements to support efficient Ca2+ release from the sarco/endoplasmic reticulum. Vascular smooth muscle cells (VSMCs) contain both TRIC subtypes and two Ca2+ release mechanisms; incidental opening of ryanodine receptors (RyRs) generates local Ca2+ sparks to induce hyperpolarization and relaxation, whereas agonist-induced activation of inositol trisphosphate receptors produces global Ca2+ transients causing contraction. Tric-a knock-out mice develop hypertension due to insufficient RyR-mediated Ca2+ sparks in VSMCs. Here we describe transgenic mice overexpressing TRIC-A channels under the control of a smooth muscle cell-specific promoter. The transgenic mice developed congenital hypotension. In Tric-a-overexpressing VSMCs from the transgenic mice, the resting membrane potential decreased because RyR-mediated Ca2+ sparks were facilitated and cell surface Ca2+-dependent K+ channels were hyperactivated. Under such hyperpolarized conditions, L-type Ca2+ channels were inactivated, and thus, the resting intracellular Ca2+ levels were reduced in Tric-a-overexpressing VSMCs. Moreover, Tric-a overexpression impaired inositol trisphosphate-sensitive stores to diminish agonist-induced Ca2+ signaling in VSMCs. These altered features likely reduced vascular tonus leading to the hypotensive phenotype. Our Tric-a-transgenic mice together with Tric-a knock-out mice indicate that TRIC-A channel density in VSMCs is responsible for controlling basal blood pressure at the whole-animal level.
- リンク情報
- ID情報
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- DOI : 10.1074/jbc.M112.435396
- ISSN : 0021-9258
- PubMed ID : 23592776
- Web of Science ID : WOS:000319822300016