Muscarinic receptors in the mammalian heart

In the mammalian heart, cardiac function is under the control of the sympat hetic and parasympathetic nervous system. All regions of the mammalian hear t are innervated by parasympathetic (vagal) nerves, although the supraventr icular tissues are more densely innervated than the ventricles. Vagal activ ation causes stimulation of cardiac muscarinic acetylcholine receptors (M-C hR) that modulate pacemaker activity via I-f and I-K,I-ACh, atrioventricula r conduction, and directly (in atrium) or indirectly (in ventricles) force of contraction. However, the functional response elicited by M-ChR-activati on depends on species, age, anatomic structure investigated, and M-ChR-agon ist concentration used. Among the five M-ChR-subtypes M-2-ChR is the predom inant isoform, present in the mammalian heart, while in the coronary circul ation M-3-ChR have been identified. In addition, evidence for a possible ex istence of an additional, not M-2-ChR in the heart has been presented. M-Ch R are subject to regulation by G-protein-coup led-receptor kinase. Alterati ons of cardiac M-2-ChR in age and various kinds of disease are discussed. ( C) 2001 Academic Press.