TRIC channels are essential for Ca2+ handling in intracellular stores.
Cell signalling requires efficient Ca2+ mobilization from intracellular stores through Ca2+ release channels, as well as predicted counter-movement of ions across the sarcoplasmic/endoplasmic reticulum membrane to balance the transient negative potential generated by Ca2+ release. Ca2+ release channels were cloned more than 15 years ago, whereas the molecular identity of putative counter-ion channels remains unknown. Here we report two TRIC (trimeric intracellular cation) channel subtypes that are differentially expressed on intracellular stores in animal cell types. TRIC subtypes contain three proposed transmembrane segments, and form homo-trimers with a bullet-like structure. Electrophysiological measurements with purified TRIC preparations identify a monovalent cation-selective channel. In TRIC-knockout mice suffering embryonic cardiac failure, mutant cardiac myocytes show severe dysfunction in intracellular Ca2+ handling. The TRIC-deficient skeletal muscle sarcoplasmic reticulum shows reduced K+ permeability, as well as altered Ca2+ 'spark' signalling and voltage-induced Ca2+ release. Therefore, TRIC channels are likely to act as counter-ion channels that function in synchronization with Ca2+ release from intracellular stores.
Yazawa
Masayuki
M
Department of Biological Chemistry, Graduate School of Pharmaceutical Sciences, Kyoto University, Kyoto 606-8501, Japan.
Ferrante
Christopher
C
Feng
Jue
J
Mio
Kazuhiro
K
Ogura
Toshihiko
T
Zhang
Miao
M
Lin
Pei-Hui
PH
Pan
Zui
Z
Komazaki
Shinji
S
Kato
Kazuhiro
K
Nishi
Miyuki
M
Zhao
Xiaoli
X
Weisleder
Noah
N
Sato
Chikara
C
Ma
Jianjie
J
Takeshima
Hiroshi
H
D000818:Animals; D002118:Calcium / Q000378:metabolism*; D020013:Calcium Signaling; D003593:Cytoplasm / Q000378:metabolism; D006321:Heart / Q000196:embryology; D007425:Intracellular Membranes / Q000378:metabolism*; D007473:Ion Channels / Q000302:isolation & purification / Q000378:metabolism*; D051379:Mice; D018345:Mice, Knockout; D008861:Microsomes / Q000378:metabolism; D008969:Molecular Sequence Data; D018482:Muscle, Skeletal / Q000378:metabolism*; D032383:Myocytes, Cardiac / Q000378:metabolism*; D010539:Permeability; D011188:Potassium / Q000378:metabolism; D011817:Rabbits; D012519:Sarcoplasmic Reticulum / Q000378:metabolism
D007473:Ion Channels; C522221:TRIC-A protein, mouse; C522222:TRIC-B protein, mouse; D011188:Potassium; D002118:Calcium