Membrane Potential Dynamics in Response to Pulsed Electric Fields: A Nanoscale Electrophysiological Study

Electrical signals play a critical role in neuronal functions and physiological processes. However, accurately characterizing subtle membrane potential changes at the cellular level remains challenging. In this study, we investigated the membrane voltage responses of undifferentiated SH-SY5Y neuroblastoma cells exposed to pulsed electric fields of 5, 10, and 20 V m^-1 at 100 Hz using conductive atomic force microscopy (CAFM). CAFM allowed for nanoscale spatial resolution and precise detection of membrane voltage alterations induced by electrical stimuli. Our results show amplitude-dependent changes in the peak-to-peak membrane voltage (ΔV = V_max - V_min) measured by CAFM in undifferentiated SH-SY5Y cells, with the largest response observed at 20 V m^-1. As a neuron-like, undifferentiated model, SH-SY5Y here is used to characterize fundamental biophysical responses to PEFs rather than to replicate mature neuronal function. These findings motivate follow-up studies in retinoic acid differentiated SH-SY5Y or primary neurons and may help refine stimulation parameters in disease-relevant models.