Human ether-a-gogo related gene (HERG) K+ channels as pharmacological targets: Present and future implications

Maurizio Taglialatela, Pasqualina Castaldo, Anna Pannaccione, Giovanna Giorgio, Lucio Annunziato

Research output: Contribution to journalArticle

56 Citations (Scopus)

Abstract

Electrophysiological and molecular biology techniques have widely expanded our knowledge of the diverse functions where K+ channels are implicated as potential and proven pharmacological targets. The aim of the present commentary is to review the recent progress in the understanding of the functional role of the K+ channels encoded by the human ether-a-gogo related gene (HERG), with particular emphasis on their direct pharmacological modulation by drugs, or on their regulation by pharmacologically relevant phenomena. About 3 years have passed since the cloning, expression, and description of the pathophysiological of HERG K+ channels in human cardiac repolarization. Despite this short lapse of time, these K+ channels have already gained considerable attention as pharmacological targets. In fact, interference with HERG K+ channels seems to be the main mechanism explaining both the therapeutic actions of the class III antiarrhythmics and the potential cardiotoxicity of second-generation H1 receptor antagonists such as terfenadine and astemizole, as well as of psychotropic drugs such as some antidepressants and neuroleptics. It seems possible to anticipate that the main tasks for future investigation will be, on the one side, the better understanding of the intimate mechanism of action of HERG K+ channel- blocking drugs in order to eculidate the conditions regulating the delicate balance between antiarrhythmic and proarrhythmic potential and, on the other, to unravel the pathophysiological role of this K+ channel in the function of the brain and of other excitable tissues.

Original languageEnglish
Pages (from-to)1741-1746
Number of pages6
JournalBiochemical Pharmacology
Volume55
Issue number11
DOIs
Publication statusPublished - Jun 1 1998

Fingerprint

Ether
Genes
Pharmacology
Astemizole
Terfenadine
Histamine H1 Receptors
Non-Sedating Histamine H1 Antagonists
Molecular biology
Cloning
Psychotropic Drugs
Pharmaceutical Preparations
Antidepressive Agents
Antipsychotic Agents
Brain
Modulation
Tissue
Organism Cloning
Molecular Biology
Therapeutics

Keywords

  • Antiarrhythmics
  • Human arrhythmias
  • Humans ether-a-gogo related gene (HERG) K channels
  • Long QT syndrome
  • Oxygen free radicals
  • Second-generation antihistamines

ASJC Scopus subject areas

  • Pharmacology

Cite this

Human ether-a-gogo related gene (HERG) K+ channels as pharmacological targets : Present and future implications. / Taglialatela, Maurizio; Castaldo, Pasqualina; Pannaccione, Anna; Giorgio, Giovanna; Annunziato, Lucio.

In: Biochemical Pharmacology, Vol. 55, No. 11, 01.06.1998, p. 1741-1746.

Research output: Contribution to journalArticle

Taglialatela, Maurizio ; Castaldo, Pasqualina ; Pannaccione, Anna ; Giorgio, Giovanna ; Annunziato, Lucio. / Human ether-a-gogo related gene (HERG) K+ channels as pharmacological targets : Present and future implications. In: Biochemical Pharmacology. 1998 ; Vol. 55, No. 11. pp. 1741-1746.
@article{000f6ac2d4e946408babfe625a1cba7a,
title = "Human ether-a-gogo related gene (HERG) K+ channels as pharmacological targets: Present and future implications",
abstract = "Electrophysiological and molecular biology techniques have widely expanded our knowledge of the diverse functions where K+ channels are implicated as potential and proven pharmacological targets. The aim of the present commentary is to review the recent progress in the understanding of the functional role of the K+ channels encoded by the human ether-a-gogo related gene (HERG), with particular emphasis on their direct pharmacological modulation by drugs, or on their regulation by pharmacologically relevant phenomena. About 3 years have passed since the cloning, expression, and description of the pathophysiological of HERG K+ channels in human cardiac repolarization. Despite this short lapse of time, these K+ channels have already gained considerable attention as pharmacological targets. In fact, interference with HERG K+ channels seems to be the main mechanism explaining both the therapeutic actions of the class III antiarrhythmics and the potential cardiotoxicity of second-generation H1 receptor antagonists such as terfenadine and astemizole, as well as of psychotropic drugs such as some antidepressants and neuroleptics. It seems possible to anticipate that the main tasks for future investigation will be, on the one side, the better understanding of the intimate mechanism of action of HERG K+ channel- blocking drugs in order to eculidate the conditions regulating the delicate balance between antiarrhythmic and proarrhythmic potential and, on the other, to unravel the pathophysiological role of this K+ channel in the function of the brain and of other excitable tissues.",
keywords = "Antiarrhythmics, Human arrhythmias, Humans ether-a-gogo related gene (HERG) K channels, Long QT syndrome, Oxygen free radicals, Second-generation antihistamines",
author = "Maurizio Taglialatela and Pasqualina Castaldo and Anna Pannaccione and Giovanna Giorgio and Lucio Annunziato",
year = "1998",
month = "6",
day = "1",
doi = "10.1016/S0006-2952(98)00002-1",
language = "English",
volume = "55",
pages = "1741--1746",
journal = "Biochemical Pharmacology",
issn = "0006-2952",
publisher = "Elsevier Inc.",
number = "11",

}

TY - JOUR

T1 - Human ether-a-gogo related gene (HERG) K+ channels as pharmacological targets

T2 - Present and future implications

AU - Taglialatela, Maurizio

AU - Castaldo, Pasqualina

AU - Pannaccione, Anna

AU - Giorgio, Giovanna

AU - Annunziato, Lucio

PY - 1998/6/1

Y1 - 1998/6/1

N2 - Electrophysiological and molecular biology techniques have widely expanded our knowledge of the diverse functions where K+ channels are implicated as potential and proven pharmacological targets. The aim of the present commentary is to review the recent progress in the understanding of the functional role of the K+ channels encoded by the human ether-a-gogo related gene (HERG), with particular emphasis on their direct pharmacological modulation by drugs, or on their regulation by pharmacologically relevant phenomena. About 3 years have passed since the cloning, expression, and description of the pathophysiological of HERG K+ channels in human cardiac repolarization. Despite this short lapse of time, these K+ channels have already gained considerable attention as pharmacological targets. In fact, interference with HERG K+ channels seems to be the main mechanism explaining both the therapeutic actions of the class III antiarrhythmics and the potential cardiotoxicity of second-generation H1 receptor antagonists such as terfenadine and astemizole, as well as of psychotropic drugs such as some antidepressants and neuroleptics. It seems possible to anticipate that the main tasks for future investigation will be, on the one side, the better understanding of the intimate mechanism of action of HERG K+ channel- blocking drugs in order to eculidate the conditions regulating the delicate balance between antiarrhythmic and proarrhythmic potential and, on the other, to unravel the pathophysiological role of this K+ channel in the function of the brain and of other excitable tissues.

AB - Electrophysiological and molecular biology techniques have widely expanded our knowledge of the diverse functions where K+ channels are implicated as potential and proven pharmacological targets. The aim of the present commentary is to review the recent progress in the understanding of the functional role of the K+ channels encoded by the human ether-a-gogo related gene (HERG), with particular emphasis on their direct pharmacological modulation by drugs, or on their regulation by pharmacologically relevant phenomena. About 3 years have passed since the cloning, expression, and description of the pathophysiological of HERG K+ channels in human cardiac repolarization. Despite this short lapse of time, these K+ channels have already gained considerable attention as pharmacological targets. In fact, interference with HERG K+ channels seems to be the main mechanism explaining both the therapeutic actions of the class III antiarrhythmics and the potential cardiotoxicity of second-generation H1 receptor antagonists such as terfenadine and astemizole, as well as of psychotropic drugs such as some antidepressants and neuroleptics. It seems possible to anticipate that the main tasks for future investigation will be, on the one side, the better understanding of the intimate mechanism of action of HERG K+ channel- blocking drugs in order to eculidate the conditions regulating the delicate balance between antiarrhythmic and proarrhythmic potential and, on the other, to unravel the pathophysiological role of this K+ channel in the function of the brain and of other excitable tissues.

KW - Antiarrhythmics

KW - Human arrhythmias

KW - Humans ether-a-gogo related gene (HERG) K channels

KW - Long QT syndrome

KW - Oxygen free radicals

KW - Second-generation antihistamines

UR - http://www.scopus.com/inward/record.url?scp=0032101646&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=0032101646&partnerID=8YFLogxK

U2 - 10.1016/S0006-2952(98)00002-1

DO - 10.1016/S0006-2952(98)00002-1

M3 - Article

C2 - 9714291

AN - SCOPUS:0032101646

VL - 55

SP - 1741

EP - 1746

JO - Biochemical Pharmacology

JF - Biochemical Pharmacology

SN - 0006-2952

IS - 11

ER -