title: Neuronal and Cardiovascular Potassium Channels as Therapeutic Drug Targets: Promise and Pitfalls.
abstract: Potassium (K(+)) channels, with their diversity, often tissue-defined distribution, and critical role in controlling cellular excitability, have long held promise of being important drug targets for the treatment of dysrhythmias in the heart and abnormal neuronal activity within the brain. With the exception of drugs that target one particular class, ATP-sensitive K(+) (KATP) channels, very few selective K(+) channel activators or inhibitors are currently licensed for clinical use in cardiovascular and neurological disease. Here we review what a range of human genetic disorders have told us about the role of specific K(+) channel subunits, explore the potential of activators and inhibitors of specific channel populations as a therapeutic strategy, and discuss possible reasons for the difficulty in designing clinically relevant K(+) channel modulators.
authors: Institute of Integrative Biology, University of Liverpool, UK.
authors: Edward S A
authors: ES
authors: Humphries
authors: Institute of Integrative Biology, University of Liverpool, UK c.dart@liv.ac.uk.
authors: Caroline
authors: C
authors: Dart
mesh_terms: D000818:Animals; D002317:Cardiovascular Agents / Q000494:pharmacology / Q000627:therapeutic use*; D002318:Cardiovascular Diseases / Q000188:drug therapy* / Q000378:metabolism; D006801:Humans; D009206:Myocardium / Q000378:metabolism; D009422:Nervous System Diseases / Q000188:drug therapy* / Q000378:metabolism; D009474:Neurons / Q000378:metabolism; D026902:Potassium Channel Blockers / Q000494:pharmacology / Q000627:therapeutic use*; D015221:Potassium Channels / Q000502:physiology*
chemical_list: D002317:Cardiovascular Agents; D026902:Potassium Channel Blockers; D015221:Potassium Channels
keywords: K+ channels; cardiac; channelopathies; drug development; ion channels; neuronal; review; vascular