Publikationsdatum:
2014-02-14
Beschreibung:
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 IP 3 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/IP 3 receptor channel functions.
Schlagwort(e):
Calcium cycling/excitation-contraction coupling, Ion channels/membrane transport
Print ISSN:
0009-7330
Digitale ISSN:
1524-4571
Thema:
Medizin
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