Abstract
Voltage-gated potassium channels (Kv channels) are the major determinants of cellular repolarization in excitable cells - they open in response to depolarization and facilitate selective efflux of potassium ions across the plasma membrane. Because of the importance of exquisitely timed cellular repolarization in controlling action potential morphology and duration, Kv channels are attractive therapeutic targets, particularly for drugs aimed at controlling aberrant electrical excitability such as is observed in cardiac arrhythmia and epilepsy. While the pore-forming a subunits of Kv channels are sufficient to form functional channels, a host of cytoplasmic and transmembrane ancillary subunits modulate their trafficking, function and regulation in vivo. Here, we consider the impact of ancillary subunits on Kv channel pharmacology, and discuss how increased understanding of the roles of ancillary subunits in native Kv channel complexes will lead to development of safer, more specific and more efficacious therapeutic small molecules.
Current Pharmaceutical Design
Title: The Impact of Ancillary Subunits on Small-Molecule Interactions with Voltage-Gated Potassium Channels
Volume: 12 Issue: 18
Author(s): Gianina Panaghie and Geoffrey W. Abbott
Affiliation:
Keywords: hERG, IKr, IKs, KChAP, KChIP, KCNE
Abstract: Voltage-gated potassium channels (Kv channels) are the major determinants of cellular repolarization in excitable cells - they open in response to depolarization and facilitate selective efflux of potassium ions across the plasma membrane. Because of the importance of exquisitely timed cellular repolarization in controlling action potential morphology and duration, Kv channels are attractive therapeutic targets, particularly for drugs aimed at controlling aberrant electrical excitability such as is observed in cardiac arrhythmia and epilepsy. While the pore-forming a subunits of Kv channels are sufficient to form functional channels, a host of cytoplasmic and transmembrane ancillary subunits modulate their trafficking, function and regulation in vivo. Here, we consider the impact of ancillary subunits on Kv channel pharmacology, and discuss how increased understanding of the roles of ancillary subunits in native Kv channel complexes will lead to development of safer, more specific and more efficacious therapeutic small molecules.
Export Options
About this article
Cite this article as:
Panaghie Gianina and Abbott W. Geoffrey, The Impact of Ancillary Subunits on Small-Molecule Interactions with Voltage-Gated Potassium Channels, Current Pharmaceutical Design 2006; 12 (18) . https://dx.doi.org/10.2174/138161206777585175
DOI https://dx.doi.org/10.2174/138161206777585175 |
Print ISSN 1381-6128 |
Publisher Name Bentham Science Publisher |
Online ISSN 1873-4286 |
- Author Guidelines
- Graphical Abstracts
- Fabricating and Stating False Information
- Research Misconduct
- Post Publication Discussions and Corrections
- Publishing Ethics and Rectitude
- Increase Visibility of Your Article
- Archiving Policies
- Peer Review Workflow
- Order Your Article Before Print
- Promote Your Article
- Manuscript Transfer Facility
- Editorial Policies
- Allegations from Whistleblowers
- Announcements
Related Articles
-
Endoplasmic Reticulum Protein Quality Control in Neurodegenerative Disease: The Good, the Bad and the Therapy
Current Medicinal Chemistry The Adverse Effects of Smoking on Health Outcomes in Bipolar Disorder: A Review and Synthesis of Biological Mechanisms
Current Molecular Medicine Recent Progress in Syntheses and Biological Activities of Kainic Acid and its Derivatives
Current Organic Chemistry Neurophysiological Alterations in the Prepsychotic Phases
Current Pharmaceutical Design Inhibitors of Multidrug Efflux Transporters: Their Membrane and Protein Interactions
Mini-Reviews in Medicinal Chemistry Overview of Childhood Epilepsy and Epileptic Syndromes and Advances in Therapy
Current Pharmaceutical Design SkQ-1 Regulates Xanthine Oxidase Activity in the Settings of Epilepsic Seizures in Rats
Neuroscience and Biomedical Engineering (Discontinued) Intranasal Drug Delivery to the Central Nervous System: Present Status and Future Outlook
Current Pharmaceutical Design Biological Activities of Quinoline Derivatives
Mini-Reviews in Medicinal Chemistry Current Status of Magnetite-Based Core@Shell Structures for Diagnosis and Therapy in Oncology Short running title: Biomedical Applications of Magnetite@Shell Structures
Current Pharmaceutical Design Synthesis and Some Reactions of 1-aryl-4-acetyl-5-methyl-1,2,3-triazole Derivatives with Anticonvulsant Activity
Mini-Reviews in Medicinal Chemistry RhoGEFs in Cell Motility: Novel Links Between Rgnef and Focal Adhesion Kinase
Current Molecular Medicine Ion Transporters in Brain Tumors
Current Medicinal Chemistry Novel Hybrid Anticonvulsants Derived from Pyrrolidine-2,5-dione Scaffold with Broad Spectrum of Activity in the Preclinical Studies
Current Topics in Medicinal Chemistry Commentary (Research Highlights: Transcranial Drug Delivery for Neurological Disorders)
CNS & Neurological Disorders - Drug Targets Revolutionary Impact of Nanodrug Delivery on Neuroscience
Current Neuropharmacology The Fragile X Family of Disorders: A Model for Autism and Targeted Treatments
Current Pediatric Reviews Purinergic Signalling: What is Missing and Needed Next? The Use of Transgenic Mice, Crystallographic Analysis and MicroRNA
CNS & Neurological Disorders - Drug Targets Pharmacological Screening of Lantana camara for its Antiallergic Activity in Rodents
Clinical Anti-Inflammatory & Anti-Allergy Drugs (Discontinued) Superior Neuroprotective Effects of Cerebrolysin in Nanoparticle-Induced Exacerbation of Hyperthermia-Induced Brain Pathology
CNS & Neurological Disorders - Drug Targets