Novel Insights into the Pervasive Role of M3 Muscarinic Receptor in Cardiac Diseases

Cardiac diseases remain the leading cause of morbidity and mortality worldwide. Heart functions are regulated by autonomic nervous systems through their transmitters and modulators, binding to cell surface receptors. Among them, the cardiac M-3 muscarinic acetylcholine receptor (M-3-mAChR) has been studied for more than 2 decades since its first discovery in mammalian heart in 1990s. The location and pathophysiological role of M-3-mAChR in the cardiovascular system have been extensively studied and many pathways involved have been uncovered. Gain-and loss-of-function studies have revealed the ubiquitous roles of M-3-mAChR in physiological and pathological conditions. Recently, many new findings have been uncovered about the relationship between M-3-mAChR and cardiac diseases, including cardiac ischemia, pathological cardiac hypertrophy, cardiac arrhythmias, cardiac conduction and heart failure. Furthermore, the novel potential cardioprotective role of M-3-mAChR against heart injury by regulation of microRNAs (miRNAs) has been revealed in the most updated research. In this review, the current new findings on the role of M-3-mAChR in heart diseases are updated, the downstream signaling pathways are summarized, perspectives and challenges of M-3-mAChR as therapeutic targets are discussed.