ABSTRACT
The ERG, EAG and ELK voltage-gated potassium channels comprise the KCNH family and are characterized by unique properties and, for ERG, well-established physiological roles. KCNHs have six transmembrane domains, with a voltage-sensor domain comprised of the S1–S4 domains and a pore domain formed from the S5, P-loop and S6 domains. KCNH subunits all have intracellular N- and C- terminal domains and a PAS domain at the N-terminus and a cyclic-nucleotide binding homology domain in the C-terminus. ERG channels encode the rapid component of the delayed-rectifier current in the heart, and help shape and repolarize cardiac action potentials. Mutations in human ERG channels are linked to long QT syndrome (LQT), which can lead to sudden cardiac death. Furthermore, the off-site inhibition of hERG by drugs leads to an acquired form of LQT, which is a common clinical problem. The physiological roles and native correlate of EAG and ELK channels are not well understood, due in part to the lack of specific channel blockers to identify the currents in native cells, but mutations in human EAG were linked to multisystem disorder symptoms including seizure and facial dysplasia. In summary, the KCNH family of channels has unique attributes and established physiological and disease roles (ERG) and emerging roles (EAG, ELK).
