Modeling the Interactions Between Sodium Channels Provides Insight Into the Negative Dominance of Certain Channel Mutations.

ABSTRACT:

Background

Na_v1.5 cardiac Na⁺ channel mutations can cause arrhythmogenic syndromes. Some of these mutations exert a dominant negative effect on wild-type channels. Recent studies showed that Na⁺ channels can dimerize, allowing coupled gating. This leads to the hypothesis that allosteric interactions between Na⁺ channels modulate their function and that these interactions may contribute to the negative dominance of certain mutations.

Methods

To investigate how allosteric interactions affect microscopic and macroscopic channel function, we developed a modeling paradigm in which Markovian models of two channels are combined. Allosteric interactions are incorporated by modifying the free energies of the composite states and/or barriers

SUBMITTER: Hichri E 

PROVIDER: S-EPMC7674773 | biostudies-literature | 2020

REPOSITORIES: biostudies-literature