Blocker escape kinetics from a membrane channel analyzed by mapping blocker diffusive dynamics onto a two-site model

Area of Science:

• Biophysics
• Physical Chemistry

Background:

• Large solute molecules entering membrane channels obstruct ion flow, causing current blockades.
• Sufficiently long molecule residence times allow for resolution of individual blockade events in single-channel experiments.

Purpose of the Study:

• To develop an analytical theory for blocker escape kinetics from membrane channels.
• To investigate the influence of external voltage bias on charged blocker survival probability within the channel.

Main Methods:

• Analytical theory development for blocker escape kinetics.
• Utilizing a two-site model for blocker dynamics.
• Deriving rate constants from a continuum diffusion model by mapping it to a two-site model.

Main Results:

• External voltage bias creates a potential well, trapping charged blockers near the channel bottleneck.
• Strong voltage bias deepens this well, significantly slowing blocker escape.
• This slow escape facilitates time-resolved observation of individual blocking events.

Conclusions:

• The developed theory accurately describes blocker escape kinetics, particularly at high biases.
• Voltage bias is a critical factor controlling the duration and observation of channel blockades.
• The two-site model, informed by continuum diffusion, provides a simplified yet effective framework for understanding blocker dynamics.