From Diffusion to the Action Potential: Building the Hodgkin-Huxley Model

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Abstract
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This lecture aims to develop the physical basis of the resting and action potentials in excitable cells. First, we will introduce the principles of chemical potential and apply them to a quantitative model of diffusion across the membrane. Using a non-polar molecule as a baseline solute, I will explain why uncharged solutes equilibrate at equal concentrations while charged species do not. From there, we will derive the Nernst equation and use it to compute equilibrium potentials for potassium and sodium under physiological concentrations, introducing the concepts of reversal potential and driving force across the phospholipid bilayer. Next, we will generalise to multiple permeant ions using the Goldman-Hodgkin-Katz (GHK) equation to predict the resting membrane potential as a weighted balance of ion permeabilities. The second half of the lecture will model the membrane as an equivalent electrical circuit, with capacitance and parallel ionic conductances that together give rise to the full current equation. This establishes the Hodgkin-Huxley framework, allowing us to describe voltage-dependent gating variables (n, m, h) and how conductances of different channels evolve in time to generate the action potential. Together, this will provide a quantitative understanding of how fundamental thermodynamic principles govern the complex electrical signalling of the nervous system - highlighting the importance of physical and mathematical modelling in biological systems.

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About the Speaker
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Dr Tanadet (Will) Pipatpolkai is a Lee Kuan Yew Postdoctoral Research Fellow at Nanyang Technological University. He completed his undergraduate studies and DPhil at the University of Oxford in the Structural Biology and Computational Biology research unit, where he used molecular dynamics simulations to study lipid interactions with ion channels under the supervision of Prof. Phillip Stansfeld and Prof. Dame Frances Ashcroft. He then moved to Stockholm for postdoctoral training at KTH Royal Institute of Technology with Prof. Lucie Delemotte, applying enhanced sampling techniques to study conformational change in ion channels. His current fellowship combines multiple simulation techniques to understand ion channels, including TMEM16A and KCa modulation and links these mechanisms to functional studies and clinical diseases.