Pannexins in the heart: cell-specific expression and contributions to disease

Heart disease is the leading cause of death globally. Although modern interventions have dramatically reduced the morbidity and mortality of heart disease, the lack of knowledge of key underlying mechanisms has limited the development of effective therapeutics. Pannexins encompass a group of three transmembrane channel-forming proteins best known for their role in purinergic signaling through the release of ATP. Pannexins, particularly pannexin 1 (Panx1), are expressed in multiple cell types throughout the heart and play a role in blood vessel regulation, immune cell recruitment and activation, and the response to ischemic injury. In this review, we analyze publicly available sequencing data to investigate the expression of pannexin proteins in human and mouse hearts at both tissue and single-cell levels. We provide a detailed review of the literature surrounding cardiac pannexin function in the context of both ischemic and non-ischemic heart disease. We then discuss the clinical use of drugs now known to target pannexin channels as a primer for the therapeutic potential of pannexins in cardiac dysfunction. Finally, we discuss the largest gaps in the current literature to guide future research.