The Sharpey-Schafer Prize Lecture was given on 24 July 2013 at IUPS 2013 in Birmingham, UK.
Sharpey-Schafer Prize Lecture
Structure and function of voltage-gated sodium channels at atomic resolution
Article first published online: 14 NOV 2013
© 2013 The Authors. Experimental Physiology © 2013 The Physiological Society
Volume 99, Issue 1, pages 35–51, January 2014
How to Cite
Catterall, W. A. (2014), Structure and function of voltage-gated sodium channels at atomic resolution. Experimental Physiology, 99: 35–51. doi: 10.1113/expphysiol.2013.071969
- Issue published online: 3 JAN 2014
- Article first published online: 14 NOV 2013
- Accepted manuscript online: 9 OCT 2013 12:11PM EST
- (Received 29 July 2013; accepted after revision 1 October 2013; first published online 4 October 2013)
- • What is the topic of this review?The central goal of the research reviewed here is to understand the functional properties of voltage-gated sodium channels at the level of high-resolution structure of the channel protein.
- • What advances does it highlight?The key functional properties of voltage-gated sodium channels, including voltage-dependent activation. Sodium conductance and selectivity, block by local anesthetics and related drugs, and both fast and slow inactivation, are now understood at the level of protein structure with high resolution. These emerging high-resolution structural models may lead to development of safer and more efficacious drugs for treatment of epilepsy, chronic pain, and cardiac arrhythmia through structure-based drug design.
Voltage-gated sodium channels initiate action potentials in nerve, muscle and other excitable cells. Early physiological studies described sodium selectivity, voltage-dependent activation and fast inactivation, and developed conceptual models for sodium channel function. This review article follows the topics of my 2013 Sharpey-Schafer Prize Lecture and gives an overview of research using a combination of biochemical, molecular biological, physiological and structural biological approaches that have elucidated the structure and function of sodium channels at the atomic level. Structural models for voltage-dependent activation, sodium selectivity and conductance, drug block and both fast and slow inactivation are discussed. A perspective for the future envisions new advances in understanding the structural basis for sodium channel function and the opportunity for structure-based discovery of novel therapeutics.