Lysosomal Transient Receptor Potential Mucolipin (TRPML) Channels in Vascular Regulation and Diseases

Transient Receptor Potential Mucolipin 1 (TRPML1) channel protein, one of the TRPML family members, is a Ca2+-permeable membrane channel with a predominant location on the late endo/lysosomes. In arterial myocytes, it has been found that this ligand-gated channel is sensitive to NAADP (Nicotinic Acid Adenine Dinucleotide Phosphate), a secondary Ca2+ messenger, to generate Ca2+ release from lysosomes followed by a global Ca2+ release response from the sarcoplasmic reticulum through Ca2+-induced Ca2+ release mechanism (CICR), which is referred to as an intracellular two-phase Ca2+ release. In coronary artery, recent studies demonstrated that NAADP-sensitive lysosomal TRPML1 channels can be activated by a variety of pro-pathogenic stimuli such as endothelin 1 (ET-1), reactive oxidative species (ROS), and death receptor ligand (FasL). The defects or derangement of the lysosomal TRPMLl channel activity have been implicated in vascular injury or diseases such as endothelial dysfunction, apoptosis and even atherosclerosis.