Nicotinic acetylcholine receptors of muscles and nerves: comparison of their structures, functional roles, and vulnerability to pathology.
There are fetal and adult subtypes of muscle nicotinic receptors (AChRs), whose structures and functional roles are reasonably well known. Mutations of their subunits cause congenital myasthenic syndromes. An autoimmune response to them causes myasthenia gravis (MG). The main immunogenic region (MIR) on muscle AChRs accounts for many aspects of the pathological mechanisms by which the autoimmune response impairs neuromuscular transmission. There are many other AChR subtypes, each defined by a different combination of subunits, some of which are transiently expressed in muscle during development, others of which are expressed in keratinocytes, vascular and bronchial epithelia, and other nonneuronal cells, as well as in a wide variety of neurons. Their varied structures and functional roles are much less well known. Mutations in subunits of some of these AChRs have thus far been associated with rare forms of epilepsy and dysautonomia, but other genetic diseases associated with them probably remain to be discovered. Autoimmune responses to some of these subunits are associated with rare dysautonomias and a skin disease. The pathological mechanisms by which these autoimmune responses impair function are much less well known than in the case of MG. AChRs may provide useful drug targets in several neurological diseases. By far, the biggest direct medical impact of AChRs is addiction to tobacco, which is mediated by nicotine acting on a variety of neuronal AChRs.
Medical School of the University of Pennsylvania, Philadelphia, Pennsylvania 19104-6074, USA. JSLKK@mail.med.upenn.edu
Jon M
JM
Lindstrom
D000818:Animals; D020274:Autoimmune Diseases of the Nervous System; D006801:Humans; D009132:Muscles / Q000378:metabolism* / Q000473:pathology; D009154:Mutation; D009157:Myasthenia Gravis / Q000235:genetics / Q000378:metabolism* / Q000503:physiopathology; D009420:Nervous System / Q000378:metabolism* / Q000473:pathology; D011978:Receptors, Nicotinic / Q000737:chemistry / Q000145:classification / Q000235:genetics / Q000502:physiology; D019966:Substance-Related Disorders
D011978:Receptors, Nicotinic