hERG | KV11.1 | Erg Related Potassium Channel Member 2
Shaker (KV1.1–KV1.8), Shab (KV2.1-KV2.2), Shaw (KV3.1–KV3.4), Shal (KV4.1–KV4.3), KQT like (KV7.1–KV7.5), Eag related (KV10.1-KV10.2), Erg related (KV11.1–KV11.3), Elk related (KV12.1)
Contains six transmembrane domains (S1–S6), four single subunits form a pore, homotetramers and heterotetramers are possible.
hERG (KV11.1) Background Information
KV11.1, better known as hERG (human Ether-à-go-go-Related Gene), contributes to the electrical activity of the heart that coordinates the heart's beating (i.e., the hERG channel mediates the repolarizing IKR current in the cardiac action potential). When this channel's ability to conduct electrical current across the cell membrane is inhibited or compromised, either by application of drugs or by rare mutations in some families, it can result in a potentially fatal disorder called long QT syndrome; a number of clinically successful drugs in the market have had the tendency to inhibit hERG, and create a concomitant risk of sudden death, as a side-effect, which has made hERG inhibition an important antitarget that must be avoided during drug development. Due to the documented potential of QT interval prolonging drugs, the United States Food and Drug Administration issued recommendations for the establishment of a cardiac safety profile during pre-clinical drug development: ICH S7B.
hERG has also been associated with modulating the functions of some cells of the nervous system and with establishing and maintaining cancer-like features in leukemic cells.
Cardiac IKR current, cell proliferation, cell migration
Long QT syndrome (LQT2), SQT1, atrial fibrillation, sudden infant death syndrome, cancer
KCNH6/ERG2, KCNH7/ERG3, ALG10B, KCNE1, KCNE2, CANX, cAMP, caveolin-1, FHL2
Terfenadine, verapamil, dofetilide, cisapride, astemizole, E4031
Patch Clamp: whole cell, room temperature, physiological temperature
Gutman et al. (2005) International Union of Pharmacology. LIII. Nomenclature and molecular relationships of voltage-gated potassium channels. Pharmacol Rev 57(4):473-508