Ion Channel Methods in Cardiovascular Safety Pharmacology

The electrical activity of the heart is the result of ions flowing through specialized proteins called ion channels. Any disruption in the normal flow of ions through these channels, such as drug block of a channel, can lead to changes in the electrocardiogram (ECG) such as PR, QRS, and QT prolongations and possibly arrhythmias. The most commonly blocked ion channel is the rapid component of the delayed rectifier (IKr) often referred to as the hERG channel. Because of the potential for a particular type of ventricular arrhythmia (torsade de pointes), regulatory agencies require an evaluation of a drug’s potential to block hERG as part of an IND (investigational new drug) submission. This chapter will discuss the various ion channels important in the heart, their pharmacology, and the current regulatory guidance for the characterization of drug effects on ion channels.