Document Type



Available under a Creative Commons Attribution Non-Commercial Share Alike 4.0 International Licence



Publication Details

Alka, K., Dolly, O.J., Ryan, B.J., and Henehan, G.T. (2014). New inhibitors of the KVB2 subunit from the mammalian potassium channels. The International Journal of Biochemistry and Cell Biology, 55, 35-39.


The role of the redox state of KVB2 subunits in the modulation of Kv1 potassium channels has been well documented over the past few years. It has been suggested that a molecule that binds to or inhibits the aldo-keto reductase activity of KVB2 might affect the modulation of channel properties. Previous studies of possible modulators of channel activity have shown that cortisone and some related compounds are able to physically dissociate the channel components by binding to a site at the interface between � and � subunits. Herein, we describe some new inhibitors of rat brain KVB2, identified using an assay based on multiple substrate turnover. This approach allows one to focus on molecules that specifically block NADPH oxidation. These studies showed that, at 0.5 mM, 3,4-dihydroxphenylacetic acid (DOPAC) was an inhibitor of Kv�2 turnover yielding a ∼40–50% reduction in the aldehyde reductase activity of this subunit. Other significant inhibitors include the bioflavinoid, rutin and the polyphenol resveratrol; some of the known cardioprotective effects of these molecules may be attributable to Kv1 channel modulation. Cortisone or catechol caused moderate inhibition of KVB2 turnover, and the aldo-keto reductases inhibitor valproate had an even smaller effect.

Despite the importance of the Kv1 channels in a number of disease states, there have been few KVB2 inhibitors reported. While the ones identified in this study are only effective at high concentrations, they could serve as tools to decipher the role of KVB2 in vivo and, eventually, inform the development of novel therapeutics.


Included in

Life Sciences Commons