Article abstract
Nature Chemical Biology 4, 708 - 714 (2008)
Published online: 21 September 2008 | doi:10.1038/nchembio.114
Cortisone dissociates the Shaker family K+ channels from their 
subunits
Yaping Pan1,2, Jun Weng1,2, Venkataraman Kabaleeswaran1, Huiguang Li1, Yu Cao1, Rahul C Bhosle1 & Ming Zhou1
Abstract
The Shaker family voltage-dependent potassium channels (Kv1) are expressed in a wide variety of cells and are essential for cellular excitability. In humans, loss-of-function mutations of Kv1 channels lead to hyperexcitability and are directly linked to episodic ataxia and atrial fibrillation. All Kv1 channels assemble with 
subunits (Kvs), and certain Kvs, for example Kv1, have an N-terminal segment that closes the channel by the N-type inactivation mechanism. In principle, dissociation of Kv1, although never reported, should eliminate inactivation and thus potentiate Kv1 current. We found that cortisone increases rat Kv1 channel activity by binding to Kv1. A crystal structure of the Kv-cortisone complex was solved to 1.82-Å resolution and revealed novel cortisone binding sites. Further studies demonstrated that cortisone promotes dissociation of Kv. The new mode of channel modulation may be explored by native or synthetic ligands to fine-tune cellular excitability.
- Department of Physiology and Cellular Biophysics, Columbia University College of Physicians and Surgeons, 630 West 168th Street, New York, New York 10032, USA.
- These authors contributed equally to this work.
Correspondence to: Ming Zhou1 e-mail: mz2140@columbia.edu
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