The acetylcholine receptor ligand-gated channel as a molecular target of disease and therapeutic agents.
Over the last two decades a convergence of techniques from various scientific disciplines has led to enormous growth in our comprehension of the structure, evolutionary trends and the multiplicity of functions performed by ligand- and voltage-gated ion channels and receptors. It is probably the combination of single-channel resolution through the introduction of the patch-clamp technique with the insights provided by genetic engineering (especially site-directed mutagenesis), that have had the clearest impact in the field by disclosing the mechanisms of action of an ever increasing number of ion channels. These large protein molecules underlie a variety of cell functions; correspondingly they can be affected by a variety of pathological conditions leading to abnormal function, either by mutation or in an acquired form. The nicotinic acetylcholine receptor (AChR), the best studied ligand-gated ion channel, is no exception to this rule, and is known to be the target of several inherited and acquired diseases. The convergence of methodological approaches that proved so successful in unraveling the normal function of ion channels in general is now being extended to include the description of pathological conditions affecting these proteins, and is already filling in hitherto missing details which will lead to improved understanding of the molecular mechanisms of channel gating, ion permeation and block in disease states affecting the receptor/channel proper or induced by exogenous ligands. More such disease states, from which mechanisms of channel function can be revealed, are likely to be discovered in the near future.
Barrantes
F J
FJ
Instituto de Investigaciones Bioquímicas de Bahía Blanca, Argentina.
D000109:Acetylcholine / Q000378:metabolism*; D006801:Humans; D015640:Ion Channel Gating; D007473:Ion Channels / Q000502:physiology*; D009154:Mutation; D009157:Myasthenia Gravis; D009422:Nervous System Diseases / Q000188:drug therapy* / Q000235:genetics*; D011950:Receptors, Cholinergic / Q000235:genetics / Q000502:physiology*; D011978:Receptors, Nicotinic / Q000502:physiology
D007473:Ion Channels; D011950:Receptors, Cholinergic; D011978:Receptors, Nicotinic; D000109:Acetylcholine