title: Trimeric intracellular cation channels and sarcoplasmic/endoplasmic reticulum calcium homeostasis.
abstract: Trimeric intracellular cation channels (TRIC) represents a novel class of trimeric intracellular cation channels. Two TRIC isoforms have been identified in both the human and the mouse genomes: TRIC-A, a subtype predominantly expressed in the sarcoplasmic reticulum (SR) of muscle cells, and TRIC-B, a ubiquitous subtype expressed in the endoplasmic reticulum (ER) of all tissues. Genetic ablation of either TRIC-A or TRIC-B leads to compromised K(+) permeation and Ca(2+) release across the SR/ER membrane, supporting the hypothesis that TRIC channels provide a counter balancing K(+) flux that reduces SR/ER membrane depolarization for maintenance of the electrochemical gradient that drives SR/ER Ca(2+) release. TRIC-A and TRIC-B seem to have differential functions in Ca(2+) signaling in excitable and nonexcitable cells. Tric-a(-/-) mice display defective Ca(2+) sparks and spontaneous transient outward currents in arterial smooth muscle and develop hypertension, in addition to skeletal muscle dysfunction. Knockout of TRIC-B results in abnormal IP3 receptor-mediated Ca(2+) release in airway epithelial cells, respiratory defects, and neonatal lethality. Double knockout mice lacking both TRIC-A and TRIC-B show embryonic lethality as a result of cardiac arrest. Such an aggravated lethality indicates that TRIC-A and TRIC-B share complementary physiological functions in Ca(2+) signaling in embryonic cardiomyocytes. Tric-a(-/-) and Tric-b(+/-) mice are viable and susceptible to stress-induced heart failure. Recent evidence suggests that TRIC-A directly modulates the function of the cardiac ryanodine receptor 2 Ca(2+) release channel, which in turn controls store-overload-induced Ca(2+) release from the SR. Thus, the TRIC channels, in addition to providing a countercurrent for SR/ER Ca(2+) release, may also function as accessory proteins that directly modulate the ryanodine receptor/IP3 receptor channel functions.
authors: From the Department of Surgery, Davis Heart and Lung Research Institute, Wexner Medical Center, The Ohio State University, Columbus (X.Z., P.L., K.H.P., J.M.); Department of Biological Chemistry, Kyoto University Graduate School of Pharmaceutical Sciences, Kyoto, Japan (D.Y., H.T.); Department of Anatomy, Saitama Medical University, Saitama, Japan (S.K.); and Departments of Physiology and Pharmacology, and Biochemistry and Molecular Biology, Libin Cardiovascular Institute of Alberta, University of Calgary, Calgary, Alberta, Canada (W.C.).
authors: Xinyu
authors: X
authors: Zhou
authors: Peihui
authors: P
authors: Lin
authors: Daiju
authors: D
authors: Yamazaki
authors: Ki Ho
authors: KH
authors: Park
authors: Shinji
authors: S
authors: Komazaki
authors: S R Wayne
authors: SR
authors: Chen
authors: Hiroshi
authors: H
authors: Takeshima
authors: Jianjie
authors: J
authors: Ma
mesh_terms: D000818:Animals; D002118:Calcium / Q000378:metabolism*; D020013:Calcium Signaling / Q000502:physiology*; D004721:Endoplasmic Reticulum / Q000502:physiology*; D006706:Homeostasis / Q000502:physiology; D006801:Humans; D007473:Ion Channels / Q000235:genetics / Q000378:metabolism*; D051379:Mice; D012519:Sarcoplasmic Reticulum / Q000502:physiology*
chemical_list: D007473:Ion Channels; C522221:TRIC-A protein, mouse; C522222:TRIC-B protein, mouse; D002118:Calcium
keywords: inositol 1,4,5-trisphosphate receptors; ryanodine receptor calcium release channel