title: TRIC-A channels in vascular smooth muscle contribute to blood pressure maintenance.
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.
authors.affiliation: Graduate School of Pharmaceutical Sciences, Kyoto University, Kyoto 606-8501, Japan.
authors.forename: Daiju
authors.initials: D
authors.lastname: Yamazaki
authors.forename: Yasuharu
authors.initials: Y
authors.lastname: Tabara
authors.forename: Satomi
authors.initials: S
authors.lastname: Kita
authors.forename: Hironori
authors.initials: H
authors.lastname: Hanada
authors.forename: Shinji
authors.initials: S
authors.lastname: Komazaki
authors.forename: Daisuke
authors.initials: D
authors.lastname: Naitou
authors.forename: Aya
authors.initials: A
authors.lastname: Mishima
authors.forename: Miyuki
authors.initials: M
authors.lastname: Nishi
authors.forename: Hisao
authors.initials: H
authors.lastname: Yamamura
authors.forename: Shinichiro
authors.initials: S
authors.lastname: Yamamoto
authors.forename: Sho
authors.initials: S
authors.lastname: Kakizawa
authors.forename: Hitoshi
authors.initials: H
authors.lastname: Miyachi
authors.forename: Shintaro
authors.initials: S
authors.lastname: Yamamoto
authors.forename: Toshiyuki
authors.initials: T
authors.lastname: Miyata
authors.forename: Yuhei
authors.initials: Y
authors.lastname: Kawano
authors.forename: Kei
authors.initials: K
authors.lastname: Kamide
authors.forename: Toshio
authors.initials: T
authors.lastname: Ogihara
authors.forename: Akira
authors.initials: A
authors.lastname: Hata
authors.forename: Satoshi
authors.initials: S
authors.lastname: Umemura
authors.forename: Masayoshi
authors.initials: M
authors.lastname: Soma
authors.forename: Norio
authors.initials: N
authors.lastname: Takahashi
authors.forename: Yuji
authors.initials: Y
authors.lastname: Imaizumi
authors.forename: Tetsuro
authors.initials: T
authors.lastname: Miki
authors.forename: Takahiro
authors.initials: T
authors.lastname: Iwamoto
authors.forename: Hiroshi
authors.initials: H
authors.lastname: Takeshima
mesh_terms: D000818:Animals; D000959:Antihypertensive Agents / Q000378:metabolism; D001794:Blood Pressure / Q000502:physiology*; D001919:Bradycardia; D002118:Calcium / Q000378:metabolism; D020013:Calcium Signaling / Q000502:physiology; D006801:Humans; D006973:Hypertension / Q000235:genetics; D053496:Inositol 1,4,5-Trisphosphate Receptors; D007473:Ion Channels / Q000235:genetics* / Q000378:metabolism*; D051379:Mice; D018345:Mice, Knockout; D009131:Muscle, Smooth, Vascular / Q000378:metabolism*; D020641:Polymorphism, Single Nucleotide; D019837:Ryanodine Receptor Calcium Release Channel / Q000378:metabolism*; D015398:Signal Transduction
chemical_list: D000959:Antihypertensive Agents; D053496:Inositol 1,4,5-Trisphosphate Receptors; D007473:Ion Channels; D019837:Ryanodine Receptor Calcium Release Channel; C522221:TRIC-A protein, mouse; D002118:Calcium