期刊
PFLUGERS ARCHIV-EUROPEAN JOURNAL OF PHYSIOLOGY
卷 465, 期 2, 页码 187-195出版社
SPRINGER HEIDELBERG
DOI: 10.1007/s00424-012-1197-5
关键词
Ca2+ release; Counter ion; Endo/sarcoplasmic reticulum; Inositol trisphosphate receptor; Intracellular Ca2+ store; Ryanodine receptor
类别
资金
- Ministry of Education, Culture, Sports, Science and Technology in Japan
- Takeda Science Foundation
- US National Institute of Health
- British Heart Foundation
- British Heart Foundation [FS/08/069/25929, RG/10/14/28576] Funding Source: researchfish
- Grants-in-Aid for Scientific Research [24659131] Funding Source: KAKEN
Trimeric intracellular cation-selective (TRIC) channel subtypes, namely TRIC-A and TRIC-B, are derived from distinct genes and distributed throughout the sarco/endoplasmic reticulum (SR/ER) and nuclear membranes. TRIC-A is preferentially expressed at high levels in excitable tissues, while TRIC-B is ubiquitously detected at relatively low levels in various tissues. TRIC channels are composed of similar to 300 amino acid residues and contain three putative membrane-spanning segments to form a bullet-shaped homo-trimeric assembly. Both native and purified recombinant TRIC subtypes form functional monovalent cation-selective channels in a lipid bilayer reconstitution system. The electrophysiological data indicate that TRIC channels behave as K+ channels under intracellular conditions, although the detailed channel characteristics remain to be investigated. The pathophysiological defects detected in knockout mice suggest that TRIC channels support SR/ER Ca2+ release mediated by ryanodine (RyR) and inositol trisphosphate receptor (IP3R) channels. For example, Tric-a-knockout mice develop hypertension resulting from vascular hypertonicity, and the mutant vascular smooth muscle cells exhibit insufficient RyR-mediated Ca2+ release for inducing hyperpolarization. Tric-b-knockout mice show respiratory failure at birth, and IP3R-mediated Ca2+ release essential for surfactant handling is impaired in the mutant alveolar epithelial cells. Moreover, double-knockout mice lacking both TRIC subtypes show embryonic heart failure, and SR Ca2+ handling is deranged in the mutant cardiomyocytes. Current evidence strongly suggests that TRIC channels mediate counter-K+ movements, in part, to facilitate physiological Ca2+ release from intracellular stores.
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