Thermophoresis induced by photothermal shock alters reversal potential and capacitance in neurons

Laser-induced thermal shock is widely encountered in neuroscience and biology, yet its effects on cellular thermodynamics remain poorly understood. Using whole-cell patch-clamp recordings paired with two-photon laser stimulation, we reveal that photothermal shock causes a pronounced depolarizing shift in the potassium channel reversal potential in cortical neurons-a deviation from classical Nernstian predictions. We propose that thermophoresis-driven ion fluxes within intra- and extracellular spaces disrupt conventional thermodynamic equilibria, necessitating a revision of the traditional Nernst formulation for reversal potential. To validate this hypothesis, we integrate thermophoretic dynamics into a Poisson-Nernst-Planck model coupled with transient thermal diffusion. Our analysis demonstrates that although thermal gradients dissipate within sub-millisecond timescales, cellular relaxation persists much longer, imparting a residual thermal memory that governs ion redistribution-an effect overlooked by standard Hodgkin-Huxley and Goldman-Hodgkin-Katz models. This extended model accurately predicts the observed depolarizing shift in potassium reversal potential following photothermal shock. Furthermore, we show that the increase in membrane capacitance-often attributed solely to thermally induced membrane deformation-can also arise from thermophoresis-mediated ionic rearrangements. Together, these findings introduce a unified biophysical model for ionic transport under thermal gradients and establish a new theoretical foundation for the principled development of next-generation photothermal neurotechnologies.