Beta-scorpion toxin effects suggest electrostatic interactions in domain II of voltage-dependent sodium channels. - Inserm - Institut national de la santé et de la recherche médicale Accéder directement au contenu
Article Dans Une Revue The Journal of Physiology Année : 2005

Beta-scorpion toxin effects suggest electrostatic interactions in domain II of voltage-dependent sodium channels.

Résumé

Beta-scorpion toxins specifically modulate the voltage dependence of sodium channel activation by acting through a voltage-sensor trapping model. We used mutagenesis, functional analysis and the action of beta-toxin as tools to investigate the existence and role in channel activation of molecular interactions between the charged residues of the S2, S3 and S4 segments in domain II of sodium channels. Mutating to arginine the acidic residues of the S2 and S3 transmembrane segments in domain II, or making charge-reversal mutation of the two outermost gating charges of the IIS4 voltage sensor, shifts the voltage dependence of channel activation to more positive potentials and enhances the effect of beta-scorpion toxin. Thus, mutations of acidic residues in IIS2 and IIS3 segments are able to promote voltage-sensor trapping in a way that is similar to the mutations of the arginines in the IIS4 segment. In order to disclose the network of interactions among acidic and basic residues we performed functional analysis of charge-inversion double mutants: our data suggest that the first arginine of the voltage sensor S4 in domain II (R850) interacts specifically with E805, D814 and E821 in the S2 and S3 segments, whereas the second arginine (R853) only interacts with D827 in the S3 segment. Our results suggest that the S2, S3 and S4 segments in domain II form a voltage-sensing structure, and that molecular interactions between the charged residues of this structure modulate the availability of the IIS4 voltage sensor for trapping by beta-toxins. They also provide unique insights into the molecular events that occur during channel activation, as well as into the structure of the channel.
Fichier principal
Vignette du fichier
Mantegazza_and_Cestele-J.Physiol.-June2005.pdf (592.47 Ko) Télécharger le fichier
Figure_1.tif (317.72 Ko) Télécharger le fichier
Figure_10.ppt (28.5 Ko) Télécharger le fichier
Figure_2.ppt (28 Ko) Télécharger le fichier
Figure_3.tif (333.44 Ko) Télécharger le fichier
Figure_4.tif (396.22 Ko) Télécharger le fichier
Figure_5.tif (400.34 Ko) Télécharger le fichier
Figure_6.tif (414.19 Ko) Télécharger le fichier
Figure_7.tif (445.06 Ko) Télécharger le fichier
Figure_8.tif (475.25 Ko) Télécharger le fichier
Figure_9.tif (214.75 Ko) Télécharger le fichier
Origine : Fichiers produits par l'(les) auteur(s)
Format : Autre
Format : Autre
Format : Autre
Format : Autre
Format : Autre
Format : Autre
Format : Autre
Format : Autre
Format : Autre
Format : Autre
Loading...

Dates et versions

inserm-00381745 , version 1 (19-06-2009)

Identifiants

Citer

Massimo Mantegazza, Sandrine Cestèle. Beta-scorpion toxin effects suggest electrostatic interactions in domain II of voltage-dependent sodium channels.: Electrostatic interactions between segments IIS2, IIS3 and IIS4 of Na+ channel.. The Journal of Physiology, 2005, 568 (Pt 1), pp.13-30. ⟨10.1113/jphysiol.2005.093484⟩. ⟨inserm-00381745⟩
126 Consultations
85 Téléchargements

Altmetric

Partager

Gmail Facebook X LinkedIn More