Pathophysiological role of omega pore current in channelopathies

Frontiers in Pharmacology
Karin Jurkat-RottFrank Lehmann-Horn

Abstract

In voltage-gated cation channels, a recurrent pattern for mutations is the neutralization of positively charged residues in the voltage-sensing S4 transmembrane segments. These mutations cause dominant ion channelopathies affecting many tissues such as brain, heart, and skeletal muscle. Recent studies suggest that the pathogenesis of associated phenotypes is not limited to alterations in the gating of the ion-conducting alpha pore. Instead, aberrant so-called omega currents, facilitated by the movement of mutated S4 segments, also appear to contribute to symptoms. Surprisingly, these omega currents conduct cations with varying ion selectivity and are activated in either a hyperpolarized or depolarized voltage range. This review gives an overview of voltage sensor channelopathies in general and focuses on pathogenesis of skeletal muscle S4 disorders for which current knowledge is most advanced.

Citations

Nov 9, 2012·Proceedings of the National Academy of Sciences of the United States of America·Pascal Gosselin-BadaroudineMohamed Chahine
Nov 19, 2013·Brain : a Journal of Neurology·Chunxiang FanKarin Jurkat-Rott
Oct 8, 2015·Biophysical Journal·Toshinori Hoshi, Clay M Armstrong
Apr 29, 2014·Frontiers in Pharmacology·Adrien MoreauMohamed Chahine
Feb 20, 2014·Brain : a Journal of Neurology·James R GroomeKarin Jurkat-Rott
Apr 11, 2018·Proceedings of the National Academy of Sciences of the United States of America·Roope MännikköAlexander A Vassilevski
Nov 9, 2017·The Journal of General Physiology·Clarisse FusterBruno Allard
May 18, 2018·Nature·Daohua JiangWilliam A Catterall
Nov 23, 2018·Channels·Alexandra PinggeraJoerg Striessnig
Jun 1, 2018·The Journal of General Physiology·Bruno Allard
Aug 19, 2015·Current Opinion in Neurology·Sophie Nicole, Bertrand Fontaine
May 30, 2020·Proceedings of the National Academy of Sciences of the United States of America·Lea WobigThomas K Berger
Oct 26, 2018·Frontiers in Cardiovascular Medicine·Adrien Moreau, Mohamed Chahine
Jun 26, 2020·Pflügers Archiv : European journal of physiology·Nadine J OrtnerJörg Striessnig
Nov 29, 2012·The Journal of Clinical Investigation·Alfred L George
Aug 28, 2020·Frontiers in Physiology·Christoph Fahlke
Mar 31, 2020·Pflügers Archiv : European journal of physiology·Bernhard E Flucher
Sep 12, 2020·Biochimica Et Biophysica Acta. Molecular Basis of Disease·Laura SoléMichael M Tamkun
Feb 12, 2021·Journal of Chemical Information and Modeling·Giulio AlberiniLuca Maragliano
Mar 19, 2021·Epilepsia·Jenna C CarpenterStephanie Schorge

Related Concepts

Trending Feeds

COVID-19

Coronaviruses encompass a large family of viruses that cause the common cold as well as more serious diseases, such as the ongoing outbreak of coronavirus disease 2019 (COVID-19; formally known as 2019-nCoV). Coronaviruses can spread from animals to humans; symptoms include fever, cough, shortness of breath, and breathing difficulties; in more severe cases, infection can lead to death. This feed covers recent research on COVID-19.

STING Receptor Agonists

Stimulator of IFN genes (STING) are a group of transmembrane proteins that are involved in the induction of type I interferon that is important in the innate immune response. The stimulation of STING has been an active area of research in the treatment of cancer and infectious diseases. Here is the latest research on STING receptor agonists.

Chronic Fatigue Syndrome

Chronic fatigue syndrome is a disease characterized by unexplained disabling fatigue; the pathology of which is incompletely understood. Discover the latest research on chronic fatigue syndrome here.

Hereditary Sensory Autonomic Neuropathy

Hereditary Sensory Autonomic Neuropathies are a group of inherited neurodegenerative disorders characterized clinically by loss of sensation and autonomic dysfunction. Here is the latest research on these neuropathies.

Glut1 Deficiency

Glut1 deficiency, an autosomal dominant, genetic metabolic disorder associated with a deficiency of GLUT1, the protein that transports glucose across the blood brain barrier, is characterized by mental and motor developmental delays and infantile seizures. Follow the latest research on Glut1 deficiency with this feed.

Regulation of Vocal-Motor Plasticity

Dopaminergic projections to the basal ganglia and nucleus accumbens shape the learning and plasticity of motivated behaviors across species including the regulation of vocal-motor plasticity and performance in songbirds. Discover the latest research on the regulation of vocal-motor plasticity here.

Neural Activity: Imaging

Imaging of neural activity in vivo has developed rapidly recently with the advancement of fluorescence microscopy, including new applications using miniaturized microscopes (miniscopes). This feed follows the progress in this growing field.

Nodding Syndrome

Nodding Syndrome is a neurological and epileptiform disorder characterized by psychomotor, mental, and growth retardation. Discover the latest research on Nodding Syndrome here.

LRRK2 & Microtubules

Mutations in the LRRK2 gene are risk-factors for developing Parkinson’s disease (PD). LRRK2 mutations in PD have been shown to enhance its association with microtubules. Here is the latest research.