TRIC-A regulates intracellular Ca²⁺ 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 Ca²⁺ 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 Ca²⁺ homeostasis. In this review article, we focus on the potential roles of TRIC-A in regulating cardiac function, particularly its effects on intracellular Ca²⁺ signaling of cardiomyocytes and discuss the current knowledge gaps.