Voltage sensing in ion channels: Mesoscale simulations of biological devices

TL;DR

This study uses mesoscale simulations to analyze the electrostatic and energetic properties of voltage sensors in ion channels, comparing different helical configurations and their responses to voltage changes.

Contribution

It introduces a simulation framework combining electrostatics and statistical mechanics to investigate voltage sensor mechanisms and their energetic responses.

Findings

Both S4 configurations show electrostatic stability.

Charge displacement is more sensitive in the -helical model.

Electrostatic energy landscapes differ by about 0.1 eV.

Abstract

Electrical signaling via voltage-gated ion channels depends upon the function of a voltage sensor (VS), identified with the S1-S4 domain in voltage-gated K+ channels. Here we investigate some energetic aspects of the sliding-helix model of the VS using simulations based on VS charges, linear dielectrics and whole-body motion. Model electrostatics in voltage-clamped boundary conditions are solved using a boundary element method. The statistical mechanical consequences of the electrostatic configurational energy are computed to gain insight into the sliding-helix mechanism and to predict experimentally measured ensemble properties such as gating charge displaced by an applied voltage. Those consequences and ensemble properties are investigated for two alternate S4 configurations, \alpha- and 3(10)-helical. Both forms of VS are found to have an inherent electrostatic stability. Maximal charge displacement is limited by geometry, specifically the range of movement where S4 charges and counter-charges overlap in the region of weak dielectric. Charge displacement responds more steeply to voltage in the \alpha-helical than the 3(10)-helical sensor. This difference is due to differences on the order of 0.1 eV in the landscapes of electrostatic energy. As a step toward integrating these VS models into a full-channel model, we include a hypothetical external load in the Hamiltonian of the system and analyze the energetic in/output relation of the VS.