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.
Weng
Jun
J
Department of Physiology and Cellular Biophysics, College of Physicians and Surgeons, Columbia University, New York, New York 10032, USA.
Cao
Yu
Y
Moss
Noah
N
Zhou
Ming
M
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