The functional impact of tissue micromotion and associated mechanical stresses on neurons and other cells in a neural interface remains unknown. Past in vivo experimental studies involving intracellular neural recordings have routinely noted membrane potential changes due to respiration and vascular pulsations. Often dismissed as an artifact, however, recent data using sharp electrodes in rodent models suggest that these changes are physiological. Previous work using gadolinium chloride, which directly and indirectly blocks mechano-sensitive ion channels and other ion channels, showed reduced micromotion-related membrane potential changes in intracellular neural recordings in vivo. This study aims to elucidate the role of mechanosensitive ion channels in micromotion related membrane potential changes. Using a double-barreled pipette, we delivered GsMTx-4 peptide (a known inhibitor of a class of mechano-sensitive ion channels) near cells experiencing micromotion related membrane potential changes. In all, we measured intracellular membrane potentials from 15 cells in one rat. Nine of 15 cells had significantly diminished respiratory-related membrane potential changes in the presence of GsMTx-4. These results indicate that mechano-sensitive ion channels may play a crucial role in modulating subthreshold electrophysiological signals at neural interfaces in response to mechanical micromotion.