Ion channels are a diverse group of pore-forming proteins that provide selective pathways for the movement of ions (Na+, K+, Ca2+, Cl−, etc) across the lipid membrane barrier. Aquaporins facilitate water movement across cell membranes in response to osmotic gradients. There is an increasing body of information on the molecular structure and functional roles of ion and water channels in health and disease, linking channel function at the molecular level to organ physiology. Because ion channels play essential roles in all cells, defects in ion channels are associated with a wide variety of pathophysiological conditions and human diseases. Diseases caused by disturbed function of ion channel subunits or regulatory proteins have been defined as “channelopathies”1, 2. In the postgenomic era the rapid progress in the molecular identification of genes for new ion channels and elucidation of their transport properties, physiological functions, and disease relevant mutations has significantly advanced the knowledge of channelopathies and potential new therapies3, 4, 5, 6, 7, 8, 9. For examples, the discovery of aquaporin water channels, a family of integral membrane proteins that selectively transport water, has led to the identification of water channelopathies including autosomal dominant and recessive forms of hereditary nepherogenic diabetes insipidus caused by aquaporin-2 mutations10, congenital cataracts incurred by aquaporin-0 mutations11 and aquired neuronal inflammatory disease neuromyelitis optica in which pathogenic autoantibodies target aquaporin-412. Impaired Cl− transport caused by mutations in genes belonging to distinct Cl− channel families has been found to cause diverse diseases such as cystic fibrosis, myotonia, epilepsy, hyperekplexia, lysosomal storage disease, deafness, renal salt loss, kidney stones, osteopetrosis, and cardiovascular diseases7, 13, 14. In addition, the studies on the role of ion channel regulatory proteins, including the sub-membrane adapter ankyrins and alpha-1 syntrophin, membrane coat protein caveolin-3, signaling platform yotiao, and lamins, have also provided novel insights into understanding of human diseases15.

In the international symposium on “Channelopathy and Drug Discovery” held in Jilin University Bethune Second Hospital, Changchun, Jilin, China on October 14–16, 2010, about 40 accomplished scientists from the United States, United Kingdom, Canada, Germany, Italy, South Korea, and different regions of China were invited to present their latest research in the fields of channelopathies, with particular focus on aquaporins and chloride channels. In facing the challenges of developing novel pharmacological therapies targeting channelopathies, new strategies of modern drug discovery, including methodology of high throughput screening from natural products and approaches of combinatorial and medicinal chemistry were also discussed. This symposium provided an important platform for domestic and overseas scientists to communicate on the latest academic achievements in channelopathies and drug discovery.

In this Special Issue of Acta Pharmacologica Sinica we have assembled a series of review articles, original research contributions, and perspectives from the speakers of the international symposium to provide the most up-to-date information on our understanding of the mechanisms of aquaporin and Cl− channelopathies and related new strategies and targets for drug discovery. To cover the topics of channelopathies other than aquaporin and Cl− channels we extended the invitation to contribute papers from several leading scientists who did not attend the symposium. These articles in this special issue impart a summary of the recent advances in the study of molecular mechanisms and functional roles of a variety of ion channels including Na+16, K+17, 18, 19, 20, Ca2+21, Cl−22, 23, 24, 25, 26, TRP27, 28, TREK29 and acid-sensing Ca2+-permeable channels30, and aquaporins31, 32, 33, 34, 35. Advances are reported in channel integrated physiology, pharmacology and pathophysiology, and in channelopathies of the nervous27, 28, 30, 34, 35, cardiovascular15, 16, 17, 18, 22, 25, 36, 37, renal20, and reproductive29, 31, 32, 33 systems. In addition, the role of pathological release of Ca2+ from the sarcoplasmic reticulum via cardiac ryanodine receptors (RyR2) in cardiac arrhythmias and RyR2 as a promising novel target for antiarrhythmic therapy are also discussed36.

We believe that publication of this special issue will also highlight the impact of Chinese scientists in this field and promote international academic exchange and collaborations to accelerate understanding of human disease mechanisms and discovery of new treatments.