| Literature DB >> 21803293 |
Daiju Yamazaki1, Yasuharu Tabara, Satomi Kita, Hironori Hanada, Shinji Komazaki, Daisuke Naitou, Aya Mishima, Miyuki Nishi, Hisao Yamamura, Shinichiro Yamamoto, Sho Kakizawa, Hitoshi Miyachi, Shintaro Yamamoto, Toshiyuki Miyata, Yuhei Kawano, Kei Kamide, Toshio Ogihara, Akira Hata, Satoshi Umemura, Masayoshi Soma, Norio Takahashi, Yuji Imaizumi, Tetsuro Miki, Takahiro Iwamoto, Hiroshi Takeshima.
Abstract
TRIC channel subtypes, namely TRIC-A and TRIC-B, are intracellular monovalent cation channels postulated to mediate counter-ion movements facilitating physiological Ca(2+) release from internal stores. Tric-a-knockout mice developed hypertension during the daytime due to enhanced myogenic tone in resistance arteries. There are two Ca(2+) release mechanisms in vascular smooth muscle cells (VSMCs); incidental opening of ryanodine receptors (RyRs) generates local Ca(2+) sparks to induce hyperpolarization, while agonist-induced activation of inositol trisphosphate receptors (IP(3)Rs) evokes global Ca(2+) transients causing contraction. Tric-a gene ablation inhibited RyR-mediated hyperpolarization signaling to stimulate voltage-dependent Ca(2+) influx, and adversely enhanced IP(3)R-mediated Ca(2+) transients by overloading Ca(2+) stores in VSMCs. Moreover, association analysis identified single-nucleotide polymorphisms (SNPs) around the human TRIC-A gene that increase hypertension risk and restrict the efficiency of antihypertensive drugs. Therefore, TRIC-A channels contribute to maintaining blood pressure, while TRIC-A SNPs could provide biomarkers for constitutional diagnosis and personalized medical treatment of essential hypertension.Entities:
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Year: 2011 PMID： 21803293 DOI： 10.1016/j.cmet.2011.05.011
Source DB: PubMed Journal: Cell Metab ISSN： 1550-4131 Impact factor: 27.287