title: Correspondences between the binding characteristics of a non-natural peptide, Lei-Dab7, and the distribution of SK subunits in the rat central nervous system.
abstract: Small-conductance calcium-activated potassium channels (SK1-SK3 channels) are responsible for long-lasting hyperpolarization following action potential and contribute to the neuronal firing and integration signal. Two peptide toxins: apamin and Leiurotoxin 1, block this SK channels with high affinities. We generated a modified Leiurotoxin 1 (Lei-Dab7) that inhibits SK2 channels with a high selectivity. Competitive binding of radio-iodinated apamin to different rat brain structures, in the presence of native apamin and Lei-Dab7, has shown that dissociation constants differ by a factor of 1000 and thus demonstrated that ligand affinity is as important as ligand selectivity for a specific receptor. However, the lack of ligands discriminating between SK channel subunits is impeding the understanding of the role of each heteromeric SK channel type in different tissues. Our study aims to better understand the molecular combinations of SK channels and their association with specific functional implications. On this purpose, a clustering technique allows us to identify five groups of brain structures reflecting singular profiles of affinity and selectivity of Lei-Dab7 in comparison with apamin. The analysis of correspondences between Lei-Dab7 binding and distribution of SK subunits in these groups of brain structures suggests that functional heteromeric SK channels are involved in specific information processes.
authors.affiliation: Unit of Functional Proteomics and Organic Food Preservation, Higher Institute of Applied Biological Sciences of Tunis, University of Tunis El Manar, Tunis, Tunisia; CNRS, Aix-Marseille Université, Laboratoire de Neurosciences Cognitives (LNC), UMR 7291, 13331 Marseille, France.
authors.forename: Sabrine
authors.initials: S
authors.lastname: Aidi-Knani
authors.affiliation: Aix Marseille Université, CNRS, NIA UMR 7260, 13331 Marseille, France.
authors.forename: Laurent
authors.initials: L
authors.lastname: Pezard
authors.affiliation: CNRS, Aix-Marseille Université, Laboratoire de Neurosciences Cognitives (LNC), UMR 7291, 13331 Marseille, France.
authors.forename: Bedel
authors.initials: B
authors.lastname: Mpari
authors.affiliation: Unit of Functional Proteomics and Organic Food Preservation, Higher Institute of Applied Biological Sciences of Tunis, University of Tunis El Manar, Tunis, Tunisia.
authors.forename: Jeannette
authors.initials: J
authors.lastname: Ben Hamida
authors.affiliation: INSERM, Aix-Marseille Université, UMRs 1097, Parc scientifique et technologique de Luminy, Marseille, France.
authors.forename: Jean-Marc
authors.initials: JM
authors.lastname: Sabatier
authors.affiliation: CNRS, Aix-Marseille Université, Laboratoire de Neurosciences Cognitives (LNC), UMR 7291, 13331 Marseille, France. Electronic address: Christiane.mourre@univ-amu.fr.
authors.forename: Christiane
authors.initials: C
authors.lastname: Mourre
authors.affiliation: Unit of Functional Proteomics and Organic Food Preservation, Higher Institute of Applied Biological Sciences of Tunis, University of Tunis El Manar, Tunis, Tunisia; Higher Institute of Environmental Sciences and Technologies, University of Carthage, Carthage, Tunisia.
authors.forename: Imed
authors.initials: I
authors.lastname: Regaya
mesh_terms: D000818:Animals; D001921:Brain / Q000378:metabolism*; D005786:Gene Expression Regulation / Q000187:drug effects; D008297:Male; D026902:Potassium Channel Blockers / Q000378:metabolism* / Q000494:pharmacology; D011485:Protein Binding; D021122:Protein Subunits / Q000037:antagonists & inhibitors / Q000378:metabolism*; D021381:Protein Transport / Q000187:drug effects; D051381:Rats; D017207:Rats, Sprague-Dawley; D012604:Scorpion Venoms / Q000378:metabolism* / Q000494:pharmacology; D051640:Small-Conductance Calcium-Activated Potassium Channels / Q000037:antagonists & inhibitors / Q000378:metabolism*; D013379:Substrate Specificity
chemical_list: D026902:Potassium Channel Blockers; D021122:Protein Subunits; D012604:Scorpion Venoms; D051640:Small-Conductance Calcium-Activated Potassium Channels; C442227:diaminobutanoyl(7)-leiurotoxin I
keywords: Apamin; Apamin (PubChem CID: 24345-16-2); Multiple correspondence analysis; Plasticity; Potassium channels; Toxins; Unsupervised clustering