Ryanodine receptors and IP₃ receptor are Ca²⁺ release channels which expressed on the endoplasmic reticulum (ER) membrane. When Ca²⁺ is released through these channels, negative charges are generated in the ER lumen. Since the negative charge inhibits further Ca²⁺ release, it has been suggested that there are counter ion channels that transport counter ions into the ER lumen to neutralize the negative charge. We have been demonstrated that TRIC (trimeric intracellular cation) channel subtypes (A and B) played critical roles in this process. TRIC-A is expressed in excitable tissues such as skeletal muscle and heart. TRIC-B is expressed universally throughout the body. In systemic Tric-b-deficient (KO) mice, type II alveolar epithelial cells are impaired in surfactant production and secretion, resulting in impaired alveolus formation and neonatal lethality. It has also been shown that osteogenesis imperfecta occurs due to impaired collagen secretion in osteoblasts. Since Tric-a and b double KO mice show embryonic lethal, both subtypes may play important functions in the heart. Since Tric-b-KO mice are neonatally lethal, we have generated cardiac-specific Tric-b-KO mice and analyzed their function. Here, we examined the effects of β-adrenergic stimulation and cardiotoxicity on mice, as well as the effects of drug-induced arrhythmia.