Potassium ion channels and human disease: phenotypes to drug targets?

A significant difficulty faced by the pharmaceutical industry is the initia l identification and selection of macromolecular targets upon which de novo drug discovery programs can be initiated. A drug target should have severa l characteristics: known biological function; robust assay systems for in v itro characterization and high-throughput screening; and be specifically mo dified by and accessible to small molecular weight compounds in vivo, ion c hannels have many of these attributes and can be viewed as suitable targets for small molecule drugs. Potassium (K+) ion channels form a large and div erse gene family responsible for critical functions in numerous cell types, tissues and organs. Recent discoveries, facilitated by genomics technologi es combined with advanced biophysical characterization methods, have identi fied novel K+ channels that are involved in important physiologic processes , or mutated in human inherited disease. These findings, coupled with a rap idly growing body of information regarding modulatory channel subunits and high resolution channel structures, are providing the critical information necessary for validation of K+ channels as drug targets.