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Cryo-EM Studies of the Cardiac Sodium Channel and Antiarrhythmic Drugs


EMSL Project ID
51781

Abstract

We plan to use cryo-EM to study the cardiac sodium channel Nav1.5 and describe its antiarrhythmic drug receptor in molecular detail. The proposed cryo-EM studies will make use of PNNL’s cutting-edge Titan Krios microscopes to perform single-particle imaging of Nav1.5 in complex with small molecules. Our previously published structures provide support for this approach though PNNL access will accelerate our studies relative to local capabilities and provide the increased resolution needed for these studies. We expect our experiments will increase understanding of cardiac physiology as well as the mechanisms of action for clinically relevant Class IA, IB, and IC antiarrhythmic drugs.

Project Details

Start Date
2020-12-15
End Date
2021-03-17
Status
Closed

Team

Principal Investigator

Michael Lenaeus
Institution
University of Washington

Team Members

Lige Tonggu
Institution
University of Washington

William Catterall
Institution
University of Washington