Trimeric intracellular cation-selective channel explained

The trimeric intracellular cation-selective channels or TRIC proteins are a group of homo-trimeric cation channel proteins of ~300 residues in the ER membrane.[1] There are two known TRIC proteins, TRIC-A and TRIC-B.

Channel function

TRICs are permeable to both Na+ and K+ but not divalent cations like Ca2+. They exhibit marked voltage-dependence, becoming more open when the cytosol is more positively charged than the ER lumen.

TRIC-A

TRIC-A is predominantly expressed in excitable tissues including brain and skeletal muscle. TRIC-A activity is thought to support RyR1-mediated efflux of Ca2+ ions from the sarcoplasmic reticulum into the cytosol.

TRIC-B

K+ flux into the ER through TRIC-B is thought to support IP3-induced efflux of Ca2+ ions through IP3-gated Ca2+ channels in the ER membrane.

Clinical significance

TRIC-A has been implicated in the regulation of arterial blood pressure through regulating the excitability of vascular smooth muscle cells. Several single-nucleotide polymorphisms (SNPs) in close proximity to the TRIC-A locus and, in future, may serve as an important biomarker in the diagnosis of essential hypertension

Null mutations in TMEM38B encoding TRIC-B are an uncommon but relatively severe cause of autosomal recessive osteogenesis imperfecta or "brittle bone disease".[2]

Notes and References

  1. Elisa. Venturi. Rebecca . Sitsapesan . Daiju . Yamazaki . Hiroshi . Takeshima . TRIC channels supporting efficient Ca2+ release from intracellular stores . European Journal of Physiology. 465. 187–195 . 15 December 2012. 2. 10.1007/s00424-012-1197-5. 23242030. 14397400 . Rebecca Sitsapesan.
  2. Wayne A. . Cabral . Masaki . Ishikawa. Matthias . Garten. Elena N. . Makareeva. Brandi M. . Sargent. MaryAnn . Weis. Aileen M. . Barnes. Emma A. . Webb. Nicholas J. . Shaw. Leena . Ala-Kokko. Felicitas L. . Lacbawan. Wolfgang . Högler. Sergey . Leikin. Paul S. . Blank. Joshua . Zimmerberg. David R. . Eyre. Yoshihiko . Yamada. Joan C. . Marini . Absence of the ER Cation Channel TMEM38B/TRIC-B Disrupts Intracellular Calcium Homeostasis and Dysregulates Collagen Synthesis in Recessive Osteogenesis Imperfecta . 10.1371/journal.pgen.1006156 . 21 July 2016 . PLOS Genetics . 12 . 7. e1006156 . 27441836 . 4956114 . free .