Zn2(+)-induced subconductance events in cardiac Na+ channels prolonged by batrachotoxin. Current-voltage behavior and single-channel kinetics

Détails

ID Serval
serval:BIB_1329A142DEAC
Type
Article: article d'un périodique ou d'un magazine.
Collection
Publications
Titre
Zn2(+)-induced subconductance events in cardiac Na+ channels prolonged by batrachotoxin. Current-voltage behavior and single-channel kinetics
Périodique
Journal of General Physiology
Auteur(s)
Schild  L., Ravindran  A., Moczydlowski  E.
ISSN
0022-1295 (Print)
Statut éditorial
Publié
Date de publication
01/1991
Volume
97
Numéro
1
Pages
117-42
Notes
In Vitro
Journal Article
Research Support, Non-U.S. Gov't
Research Support, U.S. Gov't, P.H.S. --- Old month value: Jan
Résumé
The mechanism of voltage-dependent substate production by external Zn2+ in batrachotoxin-modified Na+ channels from canine heart was investigated by analysis of the current-voltage behavior and single-channel kinetics of substate events. At the single-channel level the addition of external Zn2+ results in an increasing frequency of substate events with a mean duration of approximately 15-25 ms for the substate dwell time observed in the range of -70 to +70 mV. Under conditions of symmetrical 0.2 M NaCl, the open state of cardiac Na+ channels displays ohmic current-voltage behavior in the range of -90 to +100 mV, with a slope conductance of 21 pS. In contrast, the Zn2(+)-induced substate exhibits significant outward rectification with a slope conductance of 3.1 pS in the range of -100 to -50 mV and 5.1 pS in the range of +50 to +100 mV. Analysis of dwell-time histograms of substate events as a function of Zn2+ concentration and voltage led to the consideration of two types of models that may explain this behavior. Using a simple one-site blocking model, the apparent association rate for Zn2+ binding is more strongly voltage dependent (decreasing e-fold per +60 mV) than the Zn2+ dissociation rate (increasing e-fold per +420 mV). However, this simple blocking model cannot account for the dependence of the apparent dissociation rate on Zn2+ concentration. To explain this result, a four-state kinetic scheme involving a Zn2(+)-induced conformational change from a high conductance conformation to a substate conformation is proposed. This model, similar to one introduced by Pietrobon et al. (1989. J. Gen. Physiol. 94:1-24) for H(+)-induced substate behavior in L-type Ca2+ channels, is able to simulate the kinetic and equilibrium behavior of the primary Zn2(+)-induced substate process in heart Na+ channels. This model implies that binding of Zn2+ greatly enhances conversion of the open, ohmic channel to a low conductance conformation with an asymmetric energy profile for Na+ permeation.
Mots-clé
Animals Batrachotoxins/*pharmacology Cell Membrane/drug effects/metabolism Dogs Electrophysiology Energy Metabolism/drug effects Kinetics Models, Biological Molecular Conformation Muscles/cytology/drug effects/metabolism Sodium Channels/drug effects/*metabolism Zinc/*pharmacology
Pubmed
Web of science
Open Access
Oui
Création de la notice
24/01/2008 13:56
Dernière modification de la notice
20/08/2019 13:41
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