Modulation of potassium channels as a therapeutic approach

LAWSON, K. and MCKAY, N. (2006). Modulation of potassium channels as a therapeutic approach. Current Pharmaceutical Design, 12 (4), 459-470.

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Regulation of potassium (K+) channels evokes hyperpolarization or repolarization of the cell membrane to prevent or reverse cell excitability and is fundamental in the control of cellular activity throughout the range of tissue types within the human body. Genome projects predict that in excess of 80 K+ channel-related genes exist, resulting in a high degree of K+ channel diversity. In addition, dysfunction of K+ channels, as a result of mutations of the genes for the channel proteins or alterations in channel regulation, has been associated with the pathophysiology of diseases. These observations support K+ channels as therapeutic targets to regulate cellular homeostasis in pathophysiological conditions. Molecular cloning and expression of K+ channels offer important information in the identification of selective compounds to provide unique tissue management. Specific modulators have been identified for a limited number of K+ channel subtypes. Unfortunately the conversion of data obtained in the laboratory to success in the clinical setting has been limited. Tissue delivery of genes, in combination with drugs, may be an avenue enabling specific modulation of ion channel function and improved drug selectivity. Using specific examples (HERG, IKs, KCNQs, KCa, Kv1.3), issues regarding distribution, function and diversity related to advances made in the identification of modulators having therapeutic potential are discussed. The scope of this field is just emerging and the number of likely therapeutic indications for K+ channel modulators will increase as insight into the dynamics of expression of these channels in various diseases grows and the issue of the required selectivity is resolved.

Item Type: Article
Research Institute, Centre or Group - Does NOT include content added after October 2018: Biomedical Research Centre
Identification Number:
Page Range: 459-470
Depositing User: Jamie Young
Date Deposited: 28 May 2015 11:27
Last Modified: 18 Mar 2021 18:46

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