Deterministic principles underlying nicotinic receptor protein function

There are no available tools to verify whether current kinetic models correctly assume that the gating of ionotropic receptors is a stochastic process. Current models place no restrictions either on receptor conformational change rates or on the number of conformational states, making them insensitive to potential constraints imposed by deterministic principles. We formulate a new, deterministic model of receptor operation, providing a complete mathematical description and analyze the consequences of applying the model to the nicotinic receptor. In our model, the probability functions have narrowly defined forms with the number of parameters determined a priori. We redefine the origin of brief and long openings and introduce a state of partial desensitization. This model, in contrast to currently used kinetic models of nicotinic receptor, provides constant receptor affinity and enables the modulation of receptor activity without binding a modulator molecule.

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Publication Details

Journal
International Journal of Biological Macromolecules
Published
2025-04-06
DOI
https://doi.org/10.1016/j.ijbiomac.2025.142769
Primary Topic
Nicotinic Acetylcholine Receptors Study
Type
article
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article

Deterministic principles underlying nicotinic receptor protein function

Ewa Nurowska, Krzysztof A. Meissner
International Journal of Biological Macromolecules
Nicotinic Acetylcholine Receptors Study
article

Deterministic principles underlying nicotinic receptor protein function

Ewa Nurowska, Krzysztof A. Meissner
article en

Abstract

There are no available tools to verify whether current kinetic models correctly assume that the gating of ionotropic receptors is a stochastic process. Current models place no restrictions either on receptor conformational change rates or on the number of conformational states, making them insensitive to potential constraints imposed by deterministic principles. We formulate a new, deterministic model of receptor operation, providing a complete mathematical description and analyze the consequences of applying the model to the nicotinic receptor. In our model, the probability functions have narrowly defined forms with the number of parameters determined a priori. We redefine the origin of brief and long openings and introduce a state of partial desensitization. This model, in contrast to currently used kinetic models of nicotinic receptor, provides constant receptor affinity and enables the modulation of receptor activity without binding a modulator molecule.

International Journal of Biological MacromoleculesVol. 309(Pt 3)
Medical University of Warsaw (PL), Center for Theoretical Physics (PL)
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Nicotinic Acetylcholine Receptors Study
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