Permeation of Na+ through open and Zn(2+)-occupied conductance states of cardiac sodium channels modified by batrachotoxin: exploring ion-ion interactions in a multi-ion channel

Détails

ID Serval
serval:BIB_DD20A21694CC
Type
Article: article d'un périodique ou d'un magazine.
Collection
Publications
Titre
Permeation of Na+ through open and Zn(2+)-occupied conductance states of cardiac sodium channels modified by batrachotoxin: exploring ion-ion interactions in a multi-ion channel
Périodique
Biophysical Journal
Auteur(s)
Schild  L., Moczydlowski  E.
ISSN
0006-3495 (Print)
Statut éditorial
Publié
Date de publication
03/1994
Volume
66
Numéro
3 Pt 1
Pages
654-66
Notes
In Vitro
Journal Article
Research Support, Non-U.S. Gov't
Research Support, U.S. Gov't, P.H.S. --- Old month value: Mar
Résumé
Mammalian heart sodium channels inserted into planar bilayers exhibit a distinctive subconductance state when single batrachotoxin-modified channels are exposed to external Zn2+. The current-voltage behavior of the open state and the Zn(2+)-induced substate was characterized in the presence of symmetrical Na+ ranging from 2 to 3000 mM. The unitary conductance of the open state follows a biphasic dependence on [Na+] that can be accounted for by a 3-barrier-2-site model of Na+ permeation that includes double occupancy and Na(+)-Na+ repulsion. The unitary conductance of the Zn2+ substate follows a monophasic dependence on [Na+] that can be explained by a similar 3-barrier-2-site model with low affinity for Na+ and single occupancy due to repulsive interaction with a Zn2+ ion bound near the external entrance to the pore. The apparent association rate of Zn2+ derived from dwell-time analysis of flickering events is strongly reduced as [Na+] is raised from 50 to 500 mM. The apparent dissociation rate of Zn2+ is also enhanced as [Na+] is increased. While not excluding surface charge effects, such behavior is consistent with two types of ion-ion interactions: 1) A competitive binding interaction between Zn2+ and Na+ due to mutual competition for high affinity sites in close proximity. 2) A noncompetitive, destabilizing interaction resulting from simultaneous occupancy by Zn2+ and Na+. The repulsive influence of Zn2+ on Na+ binding in the cardiac Na+ channel is similar to that which has been proposed to occur between Ca2+ and Na+ in structurally related calcium channels. Based on recent mutagenesis data, a schematic model of functionally important residues in the external cation binding sites of calcium channels and cardiac sodium channels is proposed. In this model, the Zn(2+)-induced subconductance state results from Zn2+ binding to a site in the external vestibule that is close to the entrance of the pore but does not occlude it.
Mots-clé
Amino Acid Sequence Animals Batrachotoxins/pharmacology Binding Sites Binding, Competitive Biophysics Calcium Channels/genetics/metabolism Cattle Dogs Electric Conductivity Kinetics Lipid Bilayers/metabolism Models, Biological Molecular Sequence Data Myocardium/*metabolism Permeability Sequence Homology, Amino Acid Sodium/metabolism Sodium Channels/drug effects/genetics/*metabolism Thermodynamics Zinc/metabolism
Pubmed
Web of science
Open Access
Oui
Création de la notice
24/01/2008 13:55
Dernière modification de la notice
20/08/2019 17:01
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