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Modulation of Voltage-dependent Shaker Family Potassium Channels by an Aldo-Keto Reductase*
Jun Weng1,
Yu Cao1,
Noah Moss, , and
Ming Zhou2
Department of Physiology and Cellular Biophysics, College of Physicians and Surgeons, Columbia University, New York, New York 10032
Abstract:
The subunit (Kv) of the Shaker family voltage-dependent potassiumchannels (Kv1) is a cytosolic protein that forms a permanentcomplex with the channel. Sequence and structural conservationindicates that Kv resembles an aldo-keto reductase (AKR), anenzyme that catalyzes a redox reaction using an NADPH cofactor.A putative AKR in complex with a Kv channel has led to the hypothesisthat intracellular redox potential may dynamically influencethe excitability of a cell through Kv. Since the AKR functionof Kv has never been demonstrated, a direct functional couplingbetween the two has not been established. We report here theidentification of Kv substrates and the demonstration that Kvis a functional AKR. We have also found that channel functionis modulated when the Kv-bound NADPH is oxidized. Further studiesof the enzymatic properties of Kv seem to favor the role ofKv as a redox sensor. These results suggest that Kv may couplethe excitability of the cell to its metabolic state and presenta new avenue of research that may lead to understanding of thephysiological functions of Kv.
Received for publication December 27, 2005.
Revision received March 23, 2006.
* This work was supported by the National Multiple Sclerosis SocietyPilot Research Award, the March of Dimes Birth Defects FoundationResearch Grant 5-FY06-20, the American Heart Association GrantSDG 0630148N, and the National Institutes of Health Grant HL086392(all to M. Z.). The costs of publication of this article weredefrayed in part by the payment of page charges. This articlemust therefore be hereby marked "advertisement" in accordancewith 18 U.S.C. Section 1734 solely to indicate this fact.
This article was selected as a Paper of the Week.
1 These authors contributed equally to this work.
2 To whom correspondence should be addressed: Ming Zhou, Dept. of Physiology and Cellular Biophysics, Columbia University College of Physicians and Surgeons, 630 West 168th St., New York, NY 10032. Tel.: 212-342-3722; Fax: 212-305-5775; E-mail: mz2140{at}columbia.edu.
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This article was selected as a Paper of the Week. 
