Potassium voltage-gated channel subfamily H member 2 (hERG) and other cardiac ion channels (hERG and CICs)

Cardiac ion channels, most notably the human Ether-à-go-go-Related Gene (hERG) potassium channel, are specialized transmembrane proteins that orchestrate the electrical activity of the heart by regulating the flow of ions such as potassium, sodium, and calcium (UniProt P51787). The hERG channel (Kv11.1) is responsible for the rapid delayed rectifier potassium current (IKr), which is the primary driver of ventricular repolarization (PubMed 11114339). Other critical channels include the SCN5A-encoded sodium channel (Nav1.5) and the CACNA1C-encoded L-type calcium channel (Cav1.2), which facilitate depolarization and the action potential plateau, respectively (UniProt P35498, Q13936). While these channels are therapeutic targets for antiarrhythmic medications, they are also significant "antitargets" in drug development because unintended inhibition—particularly of hERG—can lead to delayed repolarization and QT interval prolongation (ICH S7B). This delay increases the risk of life-threatening arrhythmias, such as Torsades de Pointes, making cardiac ion channel screening a cornerstone of preclinical safety pharmacology (PubMed 12756208).

Other names

hERGKCNH2Cardiac ion channelsSCN5ACACNA1CKCNQ1Kv11.1Nav1.5Cav1.2IKrINaICa-LIKs

Drugs typically act as pore blockers or allosteric modulators that inhibit or enhance the flow of ions (K+, Na+, or Ca2+) across the cardiac cell membrane, thereby altering the duration and shape of the action potential.