Go to JCI Insight
  • About
  • Editors
  • Consulting Editors
  • For authors
  • Publication ethics
  • Publication alerts by email
  • Advertising
  • Job board
  • Contact
  • Clinical Research and Public Health
  • Current issue
  • Past issues
  • By specialty
    • COVID-19
    • Cardiology
    • Gastroenterology
    • Immunology
    • Metabolism
    • Nephrology
    • Neuroscience
    • Oncology
    • Pulmonology
    • Vascular biology
    • All ...
  • Videos
    • Conversations with Giants in Medicine
    • Video Abstracts
  • Reviews
    • View all reviews ...
    • Complement Biology and Therapeutics (May 2025)
    • Evolving insights into MASLD and MASH pathogenesis and treatment (Apr 2025)
    • Microbiome in Health and Disease (Feb 2025)
    • Substance Use Disorders (Oct 2024)
    • Clonal Hematopoiesis (Oct 2024)
    • Sex Differences in Medicine (Sep 2024)
    • Vascular Malformations (Apr 2024)
    • View all review series ...
  • Viewpoint
  • Collections
    • In-Press Preview
    • Clinical Research and Public Health
    • Research Letters
    • Letters to the Editor
    • Editorials
    • Commentaries
    • Editor's notes
    • Reviews
    • Viewpoints
    • 100th anniversary
    • Top read articles

  • Current issue
  • Past issues
  • Specialties
  • Reviews
  • Review series
  • Conversations with Giants in Medicine
  • Video Abstracts
  • In-Press Preview
  • Clinical Research and Public Health
  • Research Letters
  • Letters to the Editor
  • Editorials
  • Commentaries
  • Editor's notes
  • Reviews
  • Viewpoints
  • 100th anniversary
  • Top read articles
  • About
  • Editors
  • Consulting Editors
  • For authors
  • Publication ethics
  • Publication alerts by email
  • Advertising
  • Job board
  • Contact

Review Series

Channelopathies

Series edited by Laurie Goodman

Ion channels are pore-forming proteins that provide pathways for the controlled movement of ions into or out of cells. The processes of ionic movement across cell membranes is critical for essential and physiological processes ranging from control of the strength and duration of the heartbeat to the regulation of insulin secretion in pancreatic beta cells. Diseases caused by mutations in genes that encode ion channel subunits or regulatory proteins are referred to as channelopathies. As might be expected based on the diverse roles of ion channels, channelopathies range from inherited cardiac arrhythmias, to muscle disorders, to forms of diabetes. This series of reviews examines the roles of ion channels in health and disease.

Articles in series

The channelopathies: novel insights into molecular and genetic mechanisms of human disease
Robert S. Kass
Robert S. Kass
Published August 1, 2005
Citation Information: J Clin Invest. 2005;115(8):1986-1989. https://doi.org/10.1172/JCI26011.
View: Text | PDF

The channelopathies: novel insights into molecular and genetic mechanisms of human disease

  • Text
  • PDF
Abstract

Ion channels are pore-forming proteins that provide pathways for the controlled movement of ions into or out of cells. Ionic movement across cell membranes is critical for essential and physiological processes ranging from control of the strength and duration of the heartbeat to the regulation of insulin secretion in pancreatic β cells. Diseases caused by mutations in genes that encode ion channel subunits or regulatory proteins are referred to as channelopathies. As might be expected based on the diverse roles of ion channels, channelopathies range from inherited cardiac arrhythmias, to muscle disorders, to forms of diabetes. This series of reviews examines the roles of ion channels in health and disease.

Authors

Robert S. Kass

×

Inherited disorders of voltage-gated sodium channels
Alfred L. George Jr.
Alfred L. George Jr.
Published August 1, 2005
Citation Information: J Clin Invest. 2005;115(8):1990-1999. https://doi.org/10.1172/JCI25505.
View: Text | PDF

Inherited disorders of voltage-gated sodium channels

  • Text
  • PDF
Abstract

A variety of inherited human disorders affecting skeletal muscle contraction, heart rhythm, and nervous system function have been traced to mutations in genes encoding voltage-gated sodium channels. Clinical severity among these conditions ranges from mild or even latent disease to life-threatening or incapacitating conditions. The sodium channelopathies were among the first recognized ion channel diseases and continue to attract widespread clinical and scientific interest. An expanding knowledge base has substantially advanced our understanding of structure-function and genotype-phenotype relationships for voltage-gated sodium channels and provided new insights into the pathophysiological basis for common diseases such as cardiac arrhythmias and epilepsy.

Authors

Alfred L. George Jr.

×

Muscle channelopathies and critical points in functional and genetic studies
Karin Jurkat-Rott, Frank Lehmann-Horn
Karin Jurkat-Rott, Frank Lehmann-Horn
Published August 1, 2005
Citation Information: J Clin Invest. 2005;115(8):2000-2009. https://doi.org/10.1172/JCI25525.
View: Text | PDF

Muscle channelopathies and critical points in functional and genetic studies

  • Text
  • PDF
Abstract

Muscle channelopathies are caused by mutations in ion channel genes, by antibodies directed against ion channel proteins, or by changes of cell homeostasis leading to aberrant splicing of ion channel RNA or to disturbances of modification and localization of channel proteins. As ion channels constitute one of the only protein families that allow functional examination on the molecular level, expression studies of putative mutations have become standard in confirming that the mutations cause disease. Functional changes may not necessarily prove disease causality of a putative mutation but could be brought about by a polymorphism instead. These problems are addressed, and a more critical evaluation of the underlying genetic data is proposed.

Authors

Karin Jurkat-Rott, Frank Lehmann-Horn

×

Sodium channel mutations in epilepsy and other neurological disorders
Miriam H. Meisler, Jennifer A. Kearney
Miriam H. Meisler, Jennifer A. Kearney
Published August 1, 2005
Citation Information: J Clin Invest. 2005;115(8):2010-2017. https://doi.org/10.1172/JCI25466.
View: Text | PDF

Sodium channel mutations in epilepsy and other neurological disorders

  • Text
  • PDF
Abstract

Since the first mutations of the neuronal sodium channel SCN1A were identified 5 years ago, more than 150 mutations have been described in patients with epilepsy. Many are sporadic mutations and cause loss of function, which demonstrates haploinsufficiency of SCN1A. Mutations resulting in persistent sodium current are also common. Coding variants of SCN2A, SCN8A, and SCN9A have also been identified in patients with seizures, ataxia, and sensitivity to pain, respectively. The rapid pace of discoveries suggests that sodium channel mutations are significant factors in the etiology of neurological disease and may contribute to psychiatric disorders as well.

Authors

Miriam H. Meisler, Jennifer A. Kearney

×

Long QT syndrome: from channels to cardiac arrhythmias
Arthur J. Moss, Robert S. Kass
Arthur J. Moss, Robert S. Kass
Published August 1, 2005
Citation Information: J Clin Invest. 2005;115(8):2018-2024. https://doi.org/10.1172/JCI25537.
View: Text | PDF

Long QT syndrome: from channels to cardiac arrhythmias

  • Text
  • PDF
Abstract

Long QT syndrome, a rare genetic disorder associated with life-threatening arrhythmias, has provided a wealth of information about fundamental mechanisms underlying human cardiac electrophysiology that has come about because of truly collaborative interactions between clinical and basic scientists. Our understanding of the mechanisms that control the critical plateau and repolarization phases of the human ventricular action potential has been raised to new levels through these studies, which have clarified the manner in which both potassium and sodium channels regulate this critical period of electrical activity.

Authors

Arthur J. Moss, Robert S. Kass

×

Genetics of acquired long QT syndrome
Dan M. Roden, Prakash C. Viswanathan
Dan M. Roden, Prakash C. Viswanathan
Published August 1, 2005
Citation Information: J Clin Invest. 2005;115(8):2025-2032. https://doi.org/10.1172/JCI25539.
View: Text | PDF

Genetics of acquired long QT syndrome

  • Text
  • PDF
Abstract

The QT interval is the electrocardiographic manifestation of ventricular repolarization, is variable under physiologic conditions, and is measurably prolonged by many drugs. Rarely, however, individuals with normal base-line intervals may display exaggerated QT interval prolongation, and the potentially fatal polymorphic ventricular tachycardia torsade de pointes, with drugs or other environmental stressors such as heart block or heart failure. This review summarizes the molecular and cellular mechanisms underlying this acquired or drug-induced form of long QT syndrome, describes approaches to the analysis of a role for DNA variants in the mediation of individual susceptibility, and proposes that these concepts may be generalizable to common acquired arrhythmias.

Authors

Dan M. Roden, Prakash C. Viswanathan

×

Cardiac and skeletal muscle disorders caused by mutations in the intracellular Ca2+ release channels
Silvia G. Priori, Carlo Napolitano
Silvia G. Priori, Carlo Napolitano
Published August 1, 2005
Citation Information: J Clin Invest. 2005;115(8):2033-2038. https://doi.org/10.1172/JCI25664.
View: Text | PDF

Cardiac and skeletal muscle disorders caused by mutations in the intracellular Ca2+ release channels

  • Text
  • PDF
Abstract

Here we review the current knowledge about the mutations of the gene encoding the cardiac ryanodine receptor (RyR2) that cause cardiac arrhythmias. Similarities between the mutations identified in the RyR2 gene and those found in the gene RyR1 that cause malignant hyperthermia and central core disease are discussed. In vitro functional characterization of RyR1 and RyR2 mutants is reviewed, with a focus on the contribution that in vitro expression studies have made to our understanding of related human diseases.

Authors

Silvia G. Priori, Carlo Napolitano

×

Chloride channel diseases resulting from impaired transepithelial transport or vesicular function
Thomas J. Jentsch, … , Tanja Maritzen, Anselm A. Zdebik
Thomas J. Jentsch, … , Tanja Maritzen, Anselm A. Zdebik
Published August 1, 2005
Citation Information: J Clin Invest. 2005;115(8):2039-2046. https://doi.org/10.1172/JCI25470.
View: Text | PDF

Chloride channel diseases resulting from impaired transepithelial transport or vesicular function

  • Text
  • PDF
Abstract

The transport of anions across cellular membranes is crucial for various functions, including the control of electrical excitability of muscle and nerve, transport of salt and water across epithelia, and the regulation of cell volume or the acidification and ionic homeostasis of intracellular organelles. Given this broad range of functions, it is perhaps not surprising that mutations in Cl– channels lead to a large spectrum of diseases. These diverse pathologies include the muscle disorder myotonia, cystic fibrosis, renal salt loss in Bartter syndrome, kidney stones, deafness, and the bone disease osteopetrosis. This review will focus on diseases related to transepithelial transport and on disorders involving vesicular Cl– channels.

Authors

Thomas J. Jentsch, Tanja Maritzen, Anselm A. Zdebik

×

ATP-sensitive potassium channelopathies: focus on insulin secretion
Frances M. Ashcroft
Frances M. Ashcroft
Published August 1, 2005
Citation Information: J Clin Invest. 2005;115(8):2047-2058. https://doi.org/10.1172/JCI25495.
View: Text | PDF

ATP-sensitive potassium channelopathies: focus on insulin secretion

  • Text
  • PDF
Abstract

ATP-sensitive potassium (KATP) channels, so named because they are inhibited by intracellular ATP, play key physiological roles in many tissues. In pancreatic β cells, these channels regulate glucose-dependent insulin secretion and serve as the target for sulfonylurea drugs used to treat type 2 diabetes. This review focuses on insulin secretory disorders, such as congenital hyperinsulinemia and neonatal diabetes, that result from mutations in KATP channel genes. It also considers the extent to which defective regulation of KATP channel activity contributes to the etiology of type 2 diabetes.

Authors

Frances M. Ashcroft

×

Advertisement

Copyright © 2025 American Society for Clinical Investigation
ISSN: 0021-9738 (print), 1558-8238 (online)

Sign up for email alerts