Benzenesulfonamides act as open-channel blockers on KV3.1 potassium channel
| Autor: | Eduardo René Pérez González, Wamberto Antonio Varanda, Carlos Alberto Zanutto Bassetto Junior, Luana Vitorino Gushiken Passianoto |
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| Přispěvatelé: | Universidade Estadual Paulista (Unesp), Universidade de São Paulo (USP) |
| Rok vydání: | 2018 |
| Předmět: |
0301 basic medicine
High rate 030102 biochemistry & molecular biology Chemistry K V 3.1 Organic Chemistry Clinical Biochemistry Biochemistry Potassium channel Open-channel flow 03 medical and health sciences chemistry.chemical_compound 030104 developmental biology N-alkylbenzenesulfonamides Biophysics Open-channel blockers Action potential firing Channel blocker Patch clamp Patch-clamp Sulfanilic acid |
| Zdroj: | Scopus Repositório Institucional da UNESP Universidade Estadual Paulista (UNESP) instacron:UNESP |
| ISSN: | 1438-2199 0939-4451 |
| DOI: | 10.1007/s00726-018-2669-5 |
| Popis: | Made available in DSpace on 2019-10-06T16:03:54Z (GMT). No. of bitstreams: 0 Previous issue date: 2019-02-07 K V 3.1 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 K V 3.1 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 K V 3.1, while molecules analogous to PABA (p-aminobenzoic acid) and derived from sulfanilic acids did not block the channel. The IC 50 of six N-alkyl-benzenesulfonamides ranged from 9 to 55 µM; and the Hill coefficient suggests the binding of two molecules to block K V 3.1. Also, the effects of all molecules on K V 3.1 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 NO 2 increased the effectiveness of the blockage. Thus, we propose N-alkylbenzenesulfonamides as a new class of K V 3.1 channel blockers. Fine Organic Chemistry Laboratory Department of Chemistry and Biochemistry Faculty of Science and Technology São Paulo State University (Unesp)-Campus of Presidente Prudente Department of Physiology School of Medicine of Ribeirão Preto University of São Paulo Fine Organic Chemistry Laboratory Department of Chemistry and Biochemistry Faculty of Science and Technology São Paulo State University (Unesp)-Campus of Presidente Prudente |
| Databáze: | OpenAIRE |
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