hERG channel function: beyond long QT

Department of Neuroscience, High Throughput Biology Center and Johns Hopkins Ion Channel Center (JHICC), School of Medicine, Johns Hopkins University, 733 North Broadway, Baltimore, MD 21205, USA.
Acta Pharmacologica Sinica (Impact Factor: 2.5). 03/2013; 34(3):329-35. DOI: 10.1038/aps.2013.6
Source: PubMed

ABSTRACT To date, research on the human ether-a-go-go related gene (hERG) has focused on this potassium channel's role in cardiac repolarization and Long QT Syndrome (LQTS). However, growing evidence implicates hERG in a diversity of physiologic and pathological processes. Here we discuss these other functions of hERG, particularly their impact on diseases beyond cardiac arrhythmia.

  • [Show abstract] [Hide abstract]
    ABSTRACT: The human ether-à-go-go related gene (hERG) potassium channel is an obligatory anti-target for drug development on account of its essential role in cardiac repolarization and its close association with arrhythmia. Diverse drugs have been removed from the market owing to their inhibitory activity on the hERG channel and their contribution to acquired long QT syndrome (LQTS). Moreover, mutations that cause hERG channel dysfunction may induce congenital LQTS. Recently, an increasing number of biochemical and molecular mechanisms underlying hERG-associated LQTS have been reported. In fact, numerous potential biochemical and molecular rescue strategies are hidden within the biogenesis and regulating network. So far, rescue strategies of hERG channel dysfunction and LQTS mainly include activators, blockers, and molecules that interfere with specific links and other mechanisms. The aim of this review is to discuss the rescue strategies based on hERG channel toxicology from the biochemical and molecular perspectives.
    Acta Pharmacologica Sinica 11/2014; 35(12). DOI:10.1038/aps.2014.101 · 2.50 Impact Factor
  • Source
    [Show abstract] [Hide abstract]
    ABSTRACT: T leukemogenesis is a multistep process, where the genetic errors during T cell maturation cause the healthy progenitor to convert into the leukemic precursor that lost its ability to differentiate but possesses high potential for proliferation, self-renewal, and migration. A new misdirecting " leukemogenic " signaling network appears, composed by three types of participants which are encoded by (1) genes implicated in determined stages of T cell development but deregulated by translocations or mutations, (2) genes which normally do not participate in T cell development but are upregulated, and (3) nondifferentially expressed genes which become highly interconnected with genes expressed differentially. It appears that each of three groups may contain genes coding ion channels. In T cells, ion channels are implicated in regulation of cell cycle progression, differentiation, activation, migration, and cell death. In the present review we are going to reveal a relationship between different genetic defects, which drive the T cell neoplasias, with calcium signaling and ion channels. We suggest that changes in regulation of various ion channels in different types of the T leukemias may provide the intracellular ion microenvironment favorable to maintain self-renewal capacity, arrest differentiation, induce proliferation, and enhance motility.
    BioMed Research International 09/2014; · 2.71 Impact Factor
  • Source
    [Show abstract] [Hide abstract]
    ABSTRACT: Potassium channels are pore-forming transmembrane proteins that regulate a multitude of biological processes by controlling potassium flow across cell membranes. Aberrant potassium channel functions contribute to diseases such as epilepsy, cardiac arrhythmia, and neuromuscular symptoms collectively known as channelopathies. Increasing evidence suggests that cancer constitutes another category of channelopathies associated with dysregulated channel expression. Indeed, potassium channel-modulating agents have demonstrated antitumor efficacy. Potassium channels regulate cancer cell behaviors such as proliferation and migration through both canonical ion permeation-dependent and noncanonical ion permeation-independent functions. Given their cell surface localization and well-known pharmacology, pharmacological strategies to target potassium channel could prove to be promising cancer therapeutics.
    The Journal of General Physiology 07/2014; 206(2):151-162. DOI:10.1083/jcb.201404136 · 4.57 Impact Factor


Available from