A physical model of nicotinic ACh receptor kinetics

TL;DR

This paper introduces a new physical model for nicotinic ACh receptor kinetics, explaining variability in open event durations, receptor block, and desensitization, based on single-channel experimental data.

Contribution

It presents a novel physical model that interprets receptor open time distributions and receptor block, incorporating new theoretical derivations from probability renewal theory.

Findings

Receptor open time distribution includes three components: two brief and one long.

The model explains receptor desensitization as a natural consequence of its physical structure.

Experimental data on hydrocortisone effects support the model's predictions.

Abstract

We present a new approach to nicotinic receptor kinetics and a new model explaining random variabilities in the duration of open events. The model gives new interpretation on brief and long receptor openings and predicts (for two identical binding sites) the presence of three components in the open time distribution: two brief and a long. We also present the physical model of the receptor block. This picture naturally and universally explains receptor desensitization, the phenomenon of central importance in cellular signaling. The model is based on single-channel experiments concerning the effects of hydrocortisone (HC) on the kinetics of control wild-type (WT) and mutated alphaD200Q mouse nicotinic acetylcholine receptors (nAChRs), expressed in HEK 293 cells. The appendix contains an original result from probability renewal theory: a derivation of the probability distribution function for the duration of a process performed by two independent servers.