The Integrative Approach to Study of the Structure and Functions of Cardiac Voltage-Dependent Ion Channels

Membrane proteins, including ion channels, became the focus of structural proteomics in the mid-20 th century. The methods for studying ion channels are diverse and include structural (X-ray crystallography, cryoelectron microscopy, X-ray free electron lasers) and functional (e.g. patch clamp) methods. This review highlights the evolution of approaches to study the structure of cardiac ion channels, provides an overview of new techniques of structural biology applying to ion channels, including the use of lipo-and nanodiscs, and discusses the contribution of electrophysiological studies and molecular dynamics to obtain a complete picture of the structure and functioning of cardiac ion channels. Electrophysiological studies have become a powerful tool for deciphering the mechanisms of ion conductivity and selectivity, gating and regulation, as well as testing molecules of pharmacological interest. Obtaining of the atomic structure of ion channels was made possible by the active development of X-ray crystallography and cryoelectron microscopy, and recently by the use of XFEL.