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 bold beta subunits

Yaping Pan1,2, Jun Weng1,2, Venkataraman Kabaleeswaran1, Huiguang Li1, Yu Cao1, Rahul C Bhosle1 & Ming Zhou1


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 beta subunits (Kvbetas), and certain Kvbetas, for example Kvbeta1, have an N-terminal segment that closes the channel by the N-type inactivation mechanism. In principle, dissociation of Kvbeta1, although never reported, should eliminate inactivation and thus potentiate Kv1 current. We found that cortisone increases rat Kv1 channel activity by binding to Kvbeta1. A crystal structure of the Kvbeta-cortisone complex was solved to 1.82-Å resolution and revealed novel cortisone binding sites. Further studies demonstrated that cortisone promotes dissociation of Kvbeta. The new mode of channel modulation may be explored by native or synthetic ligands to fine-tune cellular excitability.

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  1. Department of Physiology and Cellular Biophysics, Columbia University College of Physicians and Surgeons, 630 West 168th Street, New York, New York 10032, USA.
  2. These authors contributed equally to this work.

Correspondence to: Ming Zhou1 e-mail: mz2140@columbia.edu



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