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Generalised Hodgkin-Huxley model captures human P2X and AMPA receptor currents
Alireza Poshtkohi1, Brian D Gulbransen2
1School of Physics, Engineering and Computer Science, University of Hertfordshire, Hatfield, Hertfordshire, UK.
The Journal of Physiology
|November 12, 2025
Summary
A new generalized Hodgkin-Huxley model unifies the dynamics of human ionotropic receptors, including P2X and AMPA receptors. This biophysically interpretable framework captures diverse gating kinetics for neuroscience and drug discovery applications.
Area of Science:
- Neuroscience
- Biophysics
- Computational Biology
Background:
- Ionotropic receptors regulate synaptic transmission and immune responses.
- A unified mathematical model for ionotropic receptor dynamics is currently lacking.
Purpose of the Study:
- To introduce a generalized Hodgkin-Huxley (gHH) model for human ionotropic receptors.
- To capture activation, inactivation, and recovery dynamics of P2X and AMPA receptors.
- To provide a universal, predictive framework for ion channel function.
Main Methods:
- Developed a gHH model with two activation (m1, m2) and two inactivation (h1, h2) gates.
- Incorporated receptor-specific cooperativity, binding kinetics, and desensitization.
- Proposed five distinct whole-cell current forms for gating kinetics.
Main Results:
- The gHH model accurately represents human P2X receptor family and human AMPA-type glutamate receptor dynamics.
- The model captures multi-scale temporal dynamics from milliseconds to minutes.
- Successfully replicated experimental recovery times for hP2X3 and hGluA1 receptors.
Conclusions:
- The gHH model provides a unified mathematical structure for ionotropic receptor kinetics.
- This framework is biophysically interpretable and predictive for neuroscience and drug discovery.
- Represents a step towards unified electrophysiological modeling for ion channel function in health and disease.
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