title: EPR Studies of Gating Mechanisms in Ion Channels.
abstract: Ion channels open and close in response to diverse stimuli, and the molecular events underlying these processes are extensively modulated by ligands of both endogenous and exogenous origin. In the past decade, high-resolution structures of several channel types have been solved, providing unprecedented details of the molecular architecture of these membrane proteins. Intrinsic conformational flexibility of ion channels critically governs their functions. However, the dynamics underlying gating mechanisms and modulations are obscured in the information from crystal structures. While nuclear magnetic resonance spectroscopic methods allow direct measurements of protein dynamics, they are limited by the large size of these membrane protein assemblies in detergent micelles or lipid membranes. Electron paramagnetic resonance (EPR) spectroscopy has emerged as a key biophysical tool to characterize structural dynamics of ion channels and to determine stimulus-driven conformational transition between functional states in a physiological environment. This review will provide an overview of the recent advances in the field of voltage- and ligand-gated channels and highlight some of the challenges and controversies surrounding the structural information available. It will discuss general methods used in site-directed spin labeling and EPR spectroscopy and illustrate how findings from these studies have narrowed the gap between high-resolution structures and gating mechanisms in membranes, and have thereby helped reconcile seemingly disparate models of ion channel function.
authors.affiliation: Department of Physiology and Biophysics, School of Medicine, Case Western Reserve University, Cleveland, Ohio, USA. Electronic address: sudha.chakrapani@case.edu.
authors.forename: Sudha
authors.initials: S
authors.lastname: Chakrapani
mesh_terms: D000818:Animals; D004578:Electron Spin Resonance Spectroscopy / Q000379:methods*; D006801:Humans; D015640:Ion Channel Gating; D058446:Ligand-Gated Ion Channels / Q000737:chemistry / Q000378:metabolism*; D008958:Models, Molecular; D024642:Potassium Channels, Voltage-Gated / Q000737:chemistry / Q000378:metabolism*; D011487:Protein Conformation; D061566:Voltage-Gated Sodium Channels / Q000737:chemistry / Q000378:metabolism*
chemical_list: D058446:Ligand-Gated Ion Channels; D024642:Potassium Channels, Voltage-Gated; D061566:Voltage-Gated Sodium Channels
keywords: EPR spectroscopy; Gating; Ion channels; Membrane reconstitution; Protein dynamics