Cigarette smoking is a major public health problem and has been identified as the second-most prevalent cause of death in the world. China, a country with a population of 1.3 billion, is the world's largest producer and consumer of tobacco. It estimates that there are 0.35 billion cigarette smokers in China, which bears a large proportion of the deaths attributable to smoking worldwide1. Cigarette smoking results in more than 1 000 000 premature deaths each year in China — about 1 in every 5 premature deaths2. Economically, more than $166 billion per year of total Chinese healthcare costs are attributable directly to smoking-associated diseases. If the costs of lost productivity due to smoking are added (estimated at $86 billion per year), the economic burden of smoking is more than $252 billion per year, in China alone. Recent estimates indicate that approximately one-quarter of the world's population smokes, that smoking is currently responsible for 1 in every 10 premature deaths worldwide (about 5 million deaths each year)3, and that this number will double by 2025 unless effective action is taken. Thus, there is an urgent need to reduce smoking prevalence worldwide. Unfortunately, nicotine dependence severely confounds attempts to end tobacco product use.

Nicotine is the major biologically active substance that promotes the use of tobacco products. Nicotine exerts its biological effects through nicotinic acetylcholine receptors (nAChRs). nAChRs are prototypical members of the ligand-gated ion channel superfamily of neurotransmitter receptors4. nAChRs represent both classic and contemporary models for the establishment of concepts pertaining to mechanisms of drug action, synaptic transmission, and structural/functional diversity of transmembrane signaling molecules4. Neuronal nAChRs are found throughout the central nervous system and exist as multiple, diverse subtypes of pentameric structures with unique combinations from at least twelve (α2–α10, β2–β4) genetically-distinct subunits5. Binding by endogenous (acetylcholine) or exogenous (nicotine) agonists to nAChR opens an intrinsic ion channel in the receptor, allowing the flow of cation ions (Na+, Ca2+, and K+) through the cell membrane, and inducing a wide variety of biological responses. Accumulating lines of evidence demonstrate that nAChRs play critical roles in mediating nicotine reward, dependence and addiction6, 7. In addition, alterations of nAChRs have been found in various diseases such as Parkinson's diseases, Alzheimer's disease, schizophrenia, depression, epilepsy, diabetes, respiration disorders and some immunological disorders8. Therefore, understanding the molecular biology, physiology, pharmacology and pathophysiology of neuronal nAChRs will significantly improve the diagnosis, prevention and treatment of these diseases and pathological conditions, including nicotine addiction.

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