Essential role of the TRIC-B channel in Ca2+ handling of alveolar epithelial cells and in perinatal lung maturation.
TRIC channels function as monovalent cation-specific channels that mediate counter ion movements coupled with ryanodine receptor-mediated Ca(2+) release from intracellular stores in muscle cells. Mammalian tissues differentially contain two TRIC channel subtypes: TRIC-A is abundantly expressed in excitable cells, whereas TRIC-B is ubiquitously expressed throughout tissues. Here, we report the physiological role of TRIC-B channels in mouse perinatal development. TRIC-B-knockout neonates were cyanotic owing to respiratory failure and died shortly after birth. In the mutant neonates, the deflated lungs exhibited severe histological defects, and alveolar type II epithelial cells displayed ultrastructural abnormalities. The metabolic conversion of glycogen into phospholipids was severely interrupted in the mutant type II cells, and surfactant phospholipids secreted into the alveolar space were insufficient in the mutant neonates. Moreover, the mutant type II cells were compromised for Ca(2+) release mediated by inositol-trisphosphate receptors, despite Ca(2+) overloading in intracellular stores. Our results indicate that TRIC-B channels take an active part in Ca(2+) signalling to establish specialised functions in type II cells and are thus essential for perinatal lung maturation.
Yamazaki
Daiju
D
Department of Biological Chemistry, Graduate School of Pharmaceutical Sciences, Kyoto University, Kyoto 606-8501, Japan.
Komazaki
Shinji
S
Nakanishi
Hiroki
H
Mishima
Aya
A
Nishi
Miyuki
M
Yazawa
Masayuki
M
Yamazaki
Tetsuo
T
Taguchi
Ryo
R
Takeshima
Hiroshi
H
D000818:Animals; D000831:Animals, Newborn; D020013:Calcium Signaling; D004847:Epithelial Cells / Q000378:metabolism / Q000648:ultrastructure; D005260:Female; D007473:Ion Channels / Q000172:deficiency / Q000235:genetics / Q000378:metabolism*; D008168:Lung / Q000002:abnormalities / Q000254:growth & development / Q000378:metabolism; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D046529:Microscopy, Electron, Transmission; D008954:Models, Biological; D010743:Phospholipids / Q000096:biosynthesis; D011247:Pregnancy; D011650:Pulmonary Alveoli / Q000166:cytology / Q000378:metabolism*
D007473:Ion Channels; D010743:Phospholipids; C522222:TRIC-B protein, mouse