TRIC-A channels in vascular smooth muscle contribute to blood pressure maintenance

Cell Metab. 2011 Aug 3;14(2):231-41. doi: 10.1016/j.cmet.2011.05.011.


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.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Antihypertensive Agents / metabolism
  • Blood Pressure / physiology*
  • Bradycardia
  • Calcium / metabolism
  • Calcium Signaling / physiology
  • Humans
  • Hypertension / genetics
  • Inositol 1,4,5-Trisphosphate Receptors
  • Ion Channels / genetics*
  • Ion Channels / metabolism*
  • Mice
  • Mice, Knockout
  • Muscle, Smooth, Vascular / metabolism*
  • Polymorphism, Single Nucleotide
  • Ryanodine Receptor Calcium Release Channel / metabolism*
  • Signal Transduction


  • Antihypertensive Agents
  • Inositol 1,4,5-Trisphosphate Receptors
  • Ion Channels
  • Ryanodine Receptor Calcium Release Channel
  • TRIC-A protein, mouse
  • Calcium