Incorporating the thermodynamic effects of temperature and pressure on modeling neuronal gating kinetics

Temperature and pressure affect neuronal gating kinetics. We recently used thermodynamic macro-molecular rate theory to describe the effects of temperature on the activation rate function of sodium, potassium, and calcium voltage activated conductances. Here, we extend the theory to include the effects of both, temperature and pressure. The theory includes transition changes in heat capacity, entropy, enthalpy, activation volume, expansivity, and compressibility during protein conformation. The complete model replicates experimental results from the literature. We used the expanded model to study how temperature and pressure affect the generation of action potentials in the Hodgkin-Huxley model and in detailed biophysical and morphological models of human cortical neurons. In particular, our results show how pressure can affect the optimal temperature of reaction rates and how small changes in pressure could affect spike timing and correlations across neurons. Our work provides a physics-based approach to adjust reaction rates of neuronal conductances to study cellular function in evolution and under extreme heat and pressure conditions such as those found in blast waves or electro-mechanical neuronal couplings.