TRIC-A regulates intracellular Ca homeostasis in cardiomyocytes.

Trimeric intracellular cation (TRIC) channels have been identified as monovalent cation channels that are located in the ER/SR membrane. Two isoforms discovered in mammals are TRIC-A (TMEM38a) and TRIC-B (TMEM38b). TRIC-B ubiquitously expresses in all tissues, and TRIC-B mice is lethal at the neonatal stage. TRIC-A mainly expresses in excitable cells. TRIC-A mice survive normally but show abnormal SR Ca handling in both skeletal and cardiac muscle cells. Importantly, TRIC-A mutations have been identified in human patients with stress-induced arrhythmia. In the past decade, important discoveries have been made to understand the structure and function of TRIC channels, especially its role in regulating intracellular Ca homeostasis. In this review article, we focus on the potential roles of TRIC-A in regulating cardiac function, particularly its effects on intracellular Ca signaling of cardiomyocytes and discuss the current knowledge gaps.