The Impact of Ancillary Subunits on Small-Molecule Interactions with Voltage-Gated Potassium Channels

Author(s): Gianina Panaghie, Geoffrey W. Abbott.

Journal Name: Current Pharmaceutical Design

Volume 12 , Issue 18 , 2006

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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.

Keywords: hERG, IKr, IKs, KChAP, KChIP, KCNE

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Article Details

VOLUME: 12
ISSUE: 18
Year: 2006
Page: [2285 - 2302]
Pages: 18
DOI: 10.2174/138161206777585175
Price: $58

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