Benzenesulfonamides act as open-channel blockers on KV3.1 potassium channel
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KV3.1 blockers can serve as modulators of the rate of action potential firing in neurons with high rates of firing such as those of the auditory system. We studied the effects of several bioisosteres of N-alkylbenzenesulfonamides, and molecules derived from sulfanilic acid on KV3.1 channels, heterologously expressed in L-929 cells, using the whole-cell patch-clamp technique. Only the N-alkyl-benzenesulfonamides acted as open-channel blockers on KV3.1, while molecules analogous to PABA (p-aminobenzoic acid) and derived from sulfanilic acids did not block the channel. The IC50 of six N-alkyl-benzenesulfonamides ranged from 9 to 55 µM; and the Hill coefficient suggests the binding of two molecules to block KV3.1. Also, the effects of all molecules on KV3.1 were fully reversible. We look for similar features amongst the molecules that effectively blocked the channel and used them to model a blocker prototype. We found that bulkier groups and amino-lactams decreased the effectiveness of the blockage, while the presence of NO2 increased the effectiveness of the blockage. Thus, we propose N-alkylbenzenesulfonamides as a new class of KV3.1 channel blockers.
KeywordsKV3.1 N-alkylbenzenesulfonamides Patch-clamp Open-channel blockers
We are thankful to MSc Carina Couto Martins for synthesis of benzenesulfonamide; to Dr. André Dagostin and Fernando Aguiar for technical assistance; to Dr George Chandy from the Department of Molecular Physiology at Lee Kong Chian School of Medicine, NTU (Nanyang Technological University, Singapore) for providing us the L-929 cells stably transfected with mouse KV3.1. This work was supported by Coordenação de Aperfeiçoamento de Pessoal de Nível Superior—CAPES (PhD fellowship—Carlos Alberto Zanutto Bassetto Jr.) and São Paulo State Research Foundation (FAPESP) for financial support to WAV (Grant #2012/19750-7) and ERPG (Grant #2013/24487-6).
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Conflict of interest
The authors declare that they have no conflicts of interest.
Research involving human participants and/or animals
This article does not contain any studies with human participants or animals performed by any of the authors.
This article does not contain any studies with human participants performed by any of the authors.
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