A model of mouse motor nerve excitability and the effects of polarizing currents

This study was undertaken to develop a theoretical model of mouse motor nerve excitability, and to validate it by application to recordings from mouse axons with membrane potential altered by polarizing currents. Multiple excitability tests were performed on the caudal motor nerves of 12 mice. Membrane potential was artificially modified by injecting polarizing currents through the stimulating electrodes (±20% of threshold for 1 ms pulse). A human motor nerve model was adapted to the unpolarized mouse recordings by adjusting membrane parameters to optimize the fit. To evaluate the usefulness of the model, we then determined the parameter changes which best fitted the recordings from depolarized and hyperpolarized tail nerves. The recordings from the normal axons were well fitted by a model in which axons were hyperpolarized by 4 mV, and nodal sodium and slow potassium conductances were reduced by half, compared with human median nerve motor axons. The changes with polarizing currents were qualitatively similar to those in human axons, and modeling correctly identified a change in current as the best-fitting explanation for the altered excitability. We conclude that this new model should help identify changes in membrane potential and probably in other membrane parameters in mouse models of neurological disease.