Modulation of voltage-dependent Shaker family potassium channels by an aldo-keto reductase.
The beta subunit (Kvbeta) of the Shaker family voltage-dependent potassium channels (Kv1) is a cytosolic protein that forms a permanent complex with the channel. Sequence and structural conservation indicates that Kvbeta resembles an aldo-keto reductase (AKR), an enzyme that catalyzes a redox reaction using an NADPH cofactor. A putative AKR in complex with a Kv channel has led to the hypothesis that intracellular redox potential may dynamically influence the excitability of a cell through Kvbeta. Since the AKR function of Kvbeta has never been demonstrated, a direct functional coupling between the two has not been established. We report here the identification of Kvbeta substrates and the demonstration that Kvbeta is a functional AKR. We have also found that channel function is modulated when the Kvbeta-bound NADPH is oxidized. Further studies of the enzymatic properties of Kvbeta seem to favor the role of Kvbeta as a redox sensor. These results suggest that Kvbeta may couple the excitability of the cell to its metabolic state and present a new avenue of research that may lead to understanding of the physiological functions of Kvbeta.
Department of Physiology and Cellular Biophysics, College of Physicians and Surgeons, Columbia University, New York, New York 10032, USA.
Jun
J
Weng
Yu
Y
Cao
Noah
N
Moss
Ming
M
Zhou
D000429:Alcohol Oxidoreductases / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D000449:Aldehyde Reductase; D000074408:Aldo-Keto Reductases; D000818:Animals; D005260:Female; D066298:In Vitro Techniques; D007700:Kinetics; D008958:Models, Molecular; D046912:Multiprotein Complexes; D009865:Oocytes / Q000378:metabolism; D024642:Potassium Channels, Voltage-Gated / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D051381:Rats; D011994:Recombinant Proteins / Q000737:chemistry / Q000235:genetics / Q000378:metabolism; D013379:Substrate Specificity; D014981:Xenopus
C426239:Kcnab2 protein, rat; D046912:Multiprotein Complexes; D024642:Potassium Channels, Voltage-Gated; D011994:Recombinant Proteins; D000429:Alcohol Oxidoreductases; D000074408:Aldo-Keto Reductases; D000449:Aldehyde Reductase