KCNH2 Recombinant Rabbit mAb (S-3727-63)

KCNH2 is an important member of the voltage-gated potassium channel superfamily. It consists of six transmembrane domains (S1-S6) and a pore loop located between S5 and S6, with four subunits assembling to form a functional ion channel. This channel mediates the rapid delayed rectifier potassium current (IKr) in cardiomyocytes and is characterized by high sensitivity to drug blockade and a unique "inverted rectification" property—enhanced channel opening during the late phase of action potential repolarization and under resting conditions—thereby precisely regulating the duration of the cardiac action potential and the QT interval. Dysfunction of the KCNH2 channel is the core cause of hereditary long QT syndrome type 2 (LQT2), where mutations lead to impaired channel protein maturation, reduced membrane expression, or altered gating properties, resulting in decreased IKr current density and a significantly increased risk of torsade de pointes and sudden cardiac death. Beyond cardiac function, KCNH2 is also expressed in neural stem cells and various tumor cells, influencing cell proliferation and migration through regulation of the cell cycle, apoptosis, and calcium signaling. In clinical pharmacology, due to its lack of a selective drug-binding pocket, the KCNH2 channel is a primary target for drug-induced QT interval prolongation; unintended blockade of this channel by non-cardiovascular drugs (such as antihistamines and antibiotics) is a major reason for drug withdrawal from the market. Recent studies have revealed that the N-terminal eag domain of the KCNH2 channel contains a calmodulin binding site, and the Ca²⁺/calmodulin complex can directly regulate channel deactivation kinetics, uncovering its potential regulatory role in excitation-contraction coupling. Additionally, KCNH2 channel expression is downregulated in diabetic cardiomyopathy, closely associated with hyperglycemia-induced QT prolongation. In summary, as a key regulator of cardiac repolarization, the study of KCNH2 protein not only deepens our understanding of cardiac electrophysiology but also provides a core target for drug safety assessment and arrhythmia treatment.