Abstract
Ion channels, as membrane proteins, are the sensors of the cell. They act as the first line of communication with the world beyond the plasma membrane and transduce changes in the external and internal environments into unique electrical signals to shape the responses of excitable cells. Because of their importance in cellular communication, ion channels have been intensively studied at the structural and functional levels. Here, we summarize the diverse approaches, including molecular and cellular, chemical, optical, biophysical, and computational, used to probe the structural and functional rearrangements that occur during channel activation (or sensitization), inactivation (or desensitization), and various forms of modulation. The emerging insights into the structure and function of ion channels by multidisciplinary approaches allow the development of new pharmacotherapies as well as new tools useful in controlling cellular activity.