The human ether-a-go-go related gene (hERG) potassium ion channel carries the major repolarising current in the cardiac action potential. Loss-of-function mutations of hERG result in prolongation of the cardiac QT interval and increase the risk of cardiac arrhythmias such as torsade de pointes and sudden cardiac death. Drug block of the hERG ion conduction pathway can also result in arrhythmias and sudden cardiac death. Although the first structure of the hERG channel has been published recently much of the molecular details on gating and drug binding remains unknown. We have used cryo-electron microscopy (cryo-EM) to further elucidate the mechanism of channel inactivation of the hERG potassium ion channel. We have identified several stable constructs suitable for cryo-EM and introduced point mutations to stabilize different conformations. Using an inactivation enhanced mutant we have been able to determine a structure of the hERG channel with a non-conducting selectivity filter possibly in an inactivated state. From the structure, we have located residues around the S5P helix which could be important for channel inactivation. We are investigating the role of these residues as well as the effect of ion concentration on the channel inactivation process.